| Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1 |
Dec 2012 |
7 pages |
| Authors:
Uddhav P Kelavkar; MEMORIAL UNIV MEDICAL CENTER SAVANNAH GA
|
 | FLiMP mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. To examine for the up-regulated and downregulated genes in the prostates of FLiMP we used pooled cDNA sets of individual prostate regions from FLiMP+/- and FLiMP+/+ mice and age matched nontransgenic C57BL/6 littermates were used for cDNA production. Hybridization was performed on pretreated ... |
|
| RNASEH2A -- a Putative Non-Oncogene Addiction Gene Target and Marker for Radio-sensitivity in High Risk Prostate Cancer |
Oct 2012 |
10 pages |
| Authors:
Edward M Schaeffer; Zhenhua Huang; JOHNS HOPKINS UNIV BALTIMORE MD
|
| .We proposed that RNASEH2A represents a novel type of gene, up-regulated in lethal prostate cancer to prevent catastrophic genomic instability and cell death and thereby acting to make prostate cancers resistant to treatment with radiation therapy. The major findings to date include (1) independent validation of the associate of RNASEH2A with tumor grade. (2) Identification and sample preparation of RNA specimens with lethal potential for analysis of RNAseH2a expression.(3)Observation that ... |
|
| Investigating the Role of Akt1 in Prostate Cancer Development through Phosphorylation-dependent Regulation of Skp2 Stability and Oncogenic Function |
Sep 2012 |
22 pages |
| Authors:
Wenyi Wei; Daming Gao; Hiroyuki Inuzuka; Alan Tseng; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
|
| Elevated Skp2 expression is frequently observed in many tumors including breast and prostate carcinomas. However, the molecular mechanisms underlying elevated Skp2 expression in prostate cancers have not been fully explored. Hyperactivation of the Akt pathway is considered a hallmark of many cancers and it has been reported that activation of the PI3K/Akt pathway enhances p27 destruction. Thus, we hypothesize that sustained Akt activity in prostate cancer cells leads to elevated ... |
|
| SIRT3 is a Mitochondrial Tumor Suppressor and Genetic Loss Results in a Murine Model for ER/PR-Positive Mammary Tumors Connecting Metabolism and Carcinogenesis SIRT3 is a Mitochondrial Tumor Suppressor |
Sep 2012 |
15 pages |
| Authors:
David Gius; VANDERBILT UNIV NASHVILLE TN
|
| The overarching goal of this proposal is to determine if the mitochondrial sirtuin SIRT3 is a tumor suppressor gene (TSG) that may be used to: (1) establish a murine model to investigate the mechanisms of carcinogenesis in ER/PR-positive mammary tumors; and (2) determine if SIRT3 may serve as biomarker that correlates with clinically and pathologically significant outcomes including response to therapy, local tumor control, disease free survival, and a new ... |
|
| New Approach to Identify Novel Regulators of Myc Oncoprotein Stability |
Sep 2012 |
16 pages |
| Authors:
Linda Z Penn; UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO)
|
| The Myc oncoprotein is deregulated in the majority of breast cancers yet it has not been possible to develop a therapeutic to target Myc using traditional approaches. It has recently been shown that targeting Myc for degradation may offer a new therapeutic strategy to decrease Myc levels and kill tumor cells that are addicted to this potent oncogene. Identifying Myc protein regulatory mechanisms has been a time and labor-intensive process ... |
|
| Development of a Combination Therapy for Prostate Cancer by Targeting Stat3 and HIF-1alpha |
Jul 2012 |
13 pages |
| Authors:
Naijie Jing; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| There are two signaling pathways: HIF-1alpha and Stat3 are important targets for prostate cancer (PC) therapy. HIF-1alpha is the key gene that controls the amount of the transcription of hypoxia-inducible genes. Overexpression of HIF-1alpha not only strongly enhances the rate of tumor growth and metastatic potential, but also contributes to resistance to radiotherapy and chemotherapy, leading to treatment failure and increased patient mortality. Stat3 participates in oncogenesis through the upregulation ... |
|
| Mechanism of Prostate Cancer Prevention by Down-Regulation of the GH/IGF Axis |
Jul 2012 |
13 pages |
| Authors:
Steven M Swanson; CHICAGO UNIV IL
|
| The purpose of this project was to test the hypothesis that growth hormone (GH) stimulates specific pathways, some of which are independent of IGF-I, for promoting proliferation and inhibiting death in prostate cancer cells. Our first aim is to determine which of the multiple signaling pathways stimulated by GH receptor are required to promote prostate cancer. Our strategy was to cross mice that develop prostate cancers due to a large ... |
|
| Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers |
Jun 2012 |
41 pages |
| Authors:
Zeng-Quan Yang; WAYNE STATE UNIV DETROIT MI
|
| Amplification of 8p11-12 occurs in approximately 15% of human breast cancer (HBC), and this region of amplification is significantly associated with disease-specific survival and distant recurrence in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon for identifying candidate oncogenes in breast cancer. We identified Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) as a candidate oncogene based ... |
|
| Understanding and Targeting Cell Growth Networks in Breast Cancer |
Apr 2012 |
20 pages |
| Authors:
Jason D Weber; WASHINGTON UNIV ST LOUIS MO SCHOOL OF MEDICINE
|
| In this fourth annual review, we have demonstrated that translation plays a huge role in determining tumor initiation by oncogenes. We have found that the ARF tumor suppressor is translationally regulated by mTORC1 signals and that ARF in turn negatively regulates Drosha mRNA translation. This is important because loss of Drosha results in an inability to transform immortal cells with oncogenic RasV12 alleles. This implies that Drosha provides a pro- ... |
|
| The Role of ERK1/2 in the Progression of Anti-Androgen Resistance of MtDNA Deficient Prostate Cancer |
Mar 2012 |
30 pages |
| Authors:
Cody C Cook; ARKANSAS UNIV AT LITTLE ROCK MEDICAL CENTER
|
| Characterization of the mitochondrial genomic content of normal prostatic tissue and prostate cancer tumors have revealed that the carcinogenesis of normal prostate epithelial cells to prostate cancer generates heterogeneous tumors. Within a tumor, subpopulations of cancer cells harbor mitochondria with copy numbers of the mitochondrial genome that are reduced-to-depleted, in the presence of subpopulations of cancer cells that harbor elevated copy numbers of the mitochondrial genome. In the current report, ... |
|
| The ZNF217 Breast Cancer Oncogene Amplified at 20q13: A Potential Marker for Invasiveness |
Mar 2012 |
16 pages |
| Authors:
Jeffrey P Gregg; Sheryl R Krig; CALIFORNIA UNIV DAVIS
|
| ZNF217 is found amplified at the 20q13.2 locus in 20% of breast tumors. We will explore ZNF217 over-expression as a surrogate marker for 20q13 amplification and a potential biomarker for prediction of invasive potential and metastatic disease. To examine overlap for ZNF217 amplification at 20q13 and ZNF217 overexpression, paraffin-embedded breast tissue samples have been requested and will be screened using aCGH to identify 100 samples that are 20q13-amplified. The ZNF217 ... |
|
| Chemoprevention of Prostate Cancer Initiation in a Novel Transgenic Mouse Model by Targeting 15-Lipoxygenase-1 |
Feb 2012 |
6 pages |
| Authors:
Uddhav P Kelavkar; MEMORIAL UNIV MEDICAL CENTER SAVANNAH GA
|
| FLiMP mice, which conditionally express prostatic human 15-LO-1, display mouse prostatic intraepithelial neoplasia (mPIN) by week 20, but do not progress to cancer when on normal diet. To examine for the up-regulated and downregulated genes in the prostates of FLiMP we used pooled cDNA sets of individual prostate regions from FLiMP+/- and FLiMP+/+ mice and age matched nontransgenic C57BL/6 littermates were used for cDNA production. Hybridization was performed on pretreated ... |
|
| Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer |
Feb 2012 |
14 pages |
| Authors:
Jer-Tsong Hsieh; TEXAS UNIV SOUTHWESTERN MEDICAL SCHOOL AT DALLAS
|
| Mutations in mitochondrial DNA (mtDNA) are frequent in prostate cancer and they seem to occur early during prostate malignant transformation. Depletion of mtDNA in prostate cancer cells has been linked to acquisition of androgenindependence, progression to an invasive phenotype that is resistant to conventional chemotherapies, as well as induction of epithelial-mesenchymal transition leading to cancer metastasis. Using long-range genomic polymerase chain reaction, large deletion of mtDNA can be detected in ... |
|
| Nonapoptotic Function of Caspase-6 in Promoting Mammary Carcinogenesis |
Jan 2012 |
13 pages |
| Authors:
Xiangxi Xu; MIAMI UNIV FL
|
| Malignancy is defined as the elevated mobility and invasiveness of tumor cells, and a deformed nuclear morphology is a common feature of malignant cells. We hypothesized that the decrease or absence of nesprin-1 in breast cancer cells may account for the malignant features of the neoplastic cells, the deformed nuclear morphology and invasiveness/high motility. We propose a pilot study to test this hypothesis. Indeed, we found that nesprin-1 expression is ... |
|
| Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans |
01 Oct 2011 |
52 pages |
| Authors:
Steven Dubinett; Brigette M Gomperts; Ignacio Wistuba; Avrum Spria; Pierre Massion; CALIFORNIA UNIV LOS ANGELES
|
| During our first year of research, we demonstrated a localized field cancerization phenomenon on gene expression in the airway of patients with lung cancer, and we identified several pathways preferentially activated in the airway adjacent to tumors. In addition, we have identified markers of stem cells in the airway that may represent tumor-initiating cells of the airway and are evaluating profiles of these cells. We have identified Snail as a ... |
|
| Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans |
01 Oct 2011 |
52 pages |
| Authors:
Avrum Spira; Steven Dubinett; Ignacio Wistuba; Pierre Massion; BOSTON UNIV MA
|
| During our first year of research, we demonstrated a localized field cancerization phenomenon on gene expression in the airway of patients with lung cancer, and we identified several pathways preferentially activated in the airway adjacent to tumors. In addition, we have identified markers of stem cells in the airway that may represent tumor-initiating cells of the airway and are evaluating profiles of these cells. We have identified Snail as a ... |
|
| Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans |
01 Oct 2011 |
52 pages |
| Authors:
Pierre Massion; VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
|
| During our first year of research, we demonstrated a localized field cancerization phenomenon on gene expression in the airway of patients with lung cancer, and we identified several pathways preferentially activated in the airway adjacent to tumors. In addition, we have identified markers of stem cells in the airway that may represent tumor-initiating cells of the airway and are evaluating profiles of these cells. We have identified Snail as a ... |
|
| tRNA and its Activation Targets as Biomarkers and Regulators of Breast Cancer |
Sep 2011 |
9 pages |
| Authors:
Marsha Rosner; Tao Pan; Mariana P Eternod; Donghui Zhou; Susanna Gomes; CHICAGO UNIV IL
|
| Breast cancer refers to a variety of types, each of which derives from distinct causes and merits different treatments. It is crucial to develop new classes of molecules that target heretofore unexplored cellular mechanisms so that tumors not responsive to current treatments might be responsive to new routes of therapy. We are exploring a previously underappreciated avenue that can lead to precise identification of breast cancer subtypes to improve treatment ... |
|
| EphB4 Receptor Tyrosine Kinase in Prostate Cancer |
Sep 2011 |
27 pages |
| Authors:
Nai-ying Yang; SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
|
| EphB4 is a member of the Eph family of receptor tyrosine kinases that is widely expressed in many cancer cell types. High expression of EphB4 has been positively correlated with prostate cancer malignancy. On the other hand, EphB4 has also been shown to be downregulated in other types of cancer. It is unclear how this receptor may promote or suppress oncogenesis under different circumstances. One possibility would be the Eph ... |
|
| Systematic Investigation of Key Survival and Growth Pathways in Breast Cancer |
Sep 2011 |
41 pages |
| Authors:
Junjie Chen; TEXAS UNIV SMITHVILLE MD ANDERSON CANCER CENTER
|
| We are performing proteomic studies to identify new regulators involved in the RTK/PI3K/AKT and Hippo/YAP pathways. We discovered several new regulators in these pathways, including WWP2, which targets PTEN for degradation, and AMOTL3, which associates with YAP1 and negatively regulates YAP1 activity. In the pass funding period, we also uncovered MEMO1 as an IRS1-interacting protein and showed that MEMO1 promotes epithelial-to-mesenchymal transition via regulating IRS1/Snail.. It is likely that these ... |
|
| SIRT3 is a Mitochondrial Tumor Suppressor and Genetic Loss Results in a Murine Model for ER/PR Positive Mammary Tumors Connecting Metabolism and Carcinogenesis |
Sep 2011 |
65 pages |
| Authors:
David Gius; Sarki Abdulkadir; VANDERBILT UNIV NASHVILLE TN
|
| The last year, which was funded by the DOD collaborative Breast Cancer Idea Award, has resulted in several important translational and basic science findings. Specifically, the most significant finding during the research period were: (1) the identification of MnSOD as a legitimate Sirt3 deacetylation target that for the first time shows that post-translation modifications of mitochondrial proteins plays a role in mitochondrial function (published in Molecular Cell); (2) that Sirt3 ... |
|
| The Role of elF4E Activity in Breast Cancer |
Aug 2011 |
44 pages |
| Authors:
Thomas Hughes; LEEDS UNIV (UNITED KINGDOM)
|
| Increased expression of eIF4E occurs in breast cancers and contributes to carcinogenesis by stimulating expression of cancer-related genes. However, eIF4E activity is a function of activating and inhibitory influences determined by expression and phosphorylation of eIF4E and eIF4E-binding proteins (4E-BPs). Rapamycin and everolimus are potential cancer drugs that target eIF4E indirectly by modifying 4E-BP function. Our hypothesis was that combined analyses of eIF4E and 4E-BPs would allow insights into eIF4E ... |
|
| Role of Melanin in Oncogenesis |
Aug 2011 |
18 pages |
| Authors:
Vashisht G Yennu-Nanda; M D ANDERSON CANCER CENTER HOUSTON TX
|
| Increased solar radiation and other unknown factors induce excess melanin production in melanocytes accumulated in localized areas of the skin, leading to formation of benign nevi and infrequently, dysplastic nevi that may progress to melanoma. I hypothesized that excess melanin production in melanocytes of such nevi may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including oncogenic mutations, in ... |
|
| Exploitation of Nontraditional Corp, Yacon, in Breast Cancer Prevention Using Preclinical Rat Model |
Jul 2011 |
31 pages |
| Authors:
Weiqin Jiang; COLORADO STATE UNIV FORT COLLINS
|
| Yacon has recently been introduced into farmer's markets and natural food stores in the US, but its preventive activity for breast cancer has rarely been evaluated. Objective are to determine the effect of dietary yacon on 1-methyl-1-nitrosourea (MNU) induced mammary carcinogenesis in rat; to evaluate the circulating factors and their association with the carcinogenesis; and to determine cellular signaling pathways HDAC and downstream targets - AMPK/Akt-mTOR and ghrelin-IGF1 axis. Mammary ... |
|
| Role of Foxm1 in the Pathogenesis of Prostate Cancer |
Jul 2011 |
14 pages |
| Authors:
Tanya Kalinichenko; CHILDREN'S HOSPITAL MEDICAL CENTER CINCINNATI OH
|
| The main purpose of our work is to understand the role of Foxm1 in the development of prostate cancer, provide information about molecular mechanisms whereby Foxm1 controls epithelial cell proliferation during PCa, and determine whether the inhibition of Foxm1 may potentially be beneficial during PCa therapy, therefore leading to the development of the novel therapeutic target for prostate cancer chemotherapy. During the second year of grant support, we demonstrated that ... |
|
| Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer |
01 JUN 2011 |
9 pages |
| Authors:
Kezhong Zhang; WAYNE STATE UNIV DETROIT MI
|
| Amplification of the chromosome 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify an endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of candidate oncogenes within the 8p11-12 amplicon in human breast cancer. ERLIN2 is an ER membrane protein that was recently identified as a novel mediator of ER-associated degradation. In ... |
|
| Endoplasmic Reticulum-Associated Degradation Factor ERLIN2: Oncogenic Roles and Molecular Targeting of Breast Cancer |
JUN 2011 |
9 pages |
| Authors:
Zeng-Quan Yang; WAYNE STATE UNIV DETROIT MI
|
| Amplification of the chromosome 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify an endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of candidate oncogenes within the 8p11-12 amplicon in human breast cancer. ERLIN2 is an ER membrane protein that was recently identified as a novel mediator of ER-associated degradation. In ... |
|
| Targeting mrtl to Reverse Myc in Breast Oncogenesis |
Jun 2011 |
31 pages |
| Authors:
Scott Blume; ALABAMA UNIV IN BIRMINGHAM
|
| Our lab has discovered a 15 kDa protein, designated mrtl (myc-related translation / localization regulatory factor), which is generated from the same mRNA as c-Myc. We found that mrtl may be capable of direct interaction with the c-myc mRNA, and that ectopic overexpression of mrtl is associated with loss of Myc from the nucleus. Based on these results, we hypothesized that: (a) mrtl may regulate Myc translation and localization to ... |
|
| Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases |
MAY 2011 |
21 pages |
| Authors:
Xiankai Sun; TEXAS UNIV AT DALLAS
|
| The ultimate goal of this project is to develop specific PET imaging probes for early detection of distal metastases of prostate cancer. Based on one of our studies using a polyarginine (NH2GR11) to deliver a therapeutic moiety to various prostate cancer cell lines, we hypothesize a new group of prostate-specific peptides could be developed as novel PET imaging probes using NH2GR11 as a lead compound for the detection of multi-foci ... |
|
| Suppression of BRCA2 by Mutant Mitochondrial DNA in Prostate Cancer |
May 2011 |
31 pages |
| Authors:
Jer-Tsong Hsieh; TEXAS UNIV AT DALLAS SOUTHWESTERN MEDICAL CENTER
|
| Mutations in mitochondrial DNA (mtDNA) are frequent in prostate cancer and they seem to occur early during prostate malignant transformation. Depletion of mtDNA in prostate cancer cells has been linked to acquisition of androgen-independence, progression to an invasive phenotype that is resistant to conventional chemotherapies, as well as induction of epithelialmesenchymal transition leading to cancer metastasis. Using long-range genomic polymerase chain reaction, large deletion of mtDNA can be detected in ... |
|
| Role of Cyclin E as an Early Event in Ovarian Carcinogenesis |
APR 2011 |
40 pages |
| Authors:
Christine Walsh; CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA
|
| At the genetic level, ovarian cancer is characterized by a large degree of genetic instability. High copy-number amplification at the CCNE1 (cyclin E) gene locus is the single most notable recurrent change, occurring in about 20% of tumors. We have hypothesized that CCNE1 gene amplification is an initiating event in the carcinogenic process of a subset of epithelial ovarian cancers. In the first two years of this award, we have ... |
|
| The Infectious Pathogenesis Of Prostate Cancer |
Apr 2011 |
55 pages |
| Authors:
Hans-Olov Adami; Lorelei Mucci; HARVARD SCHOOL OF PUBLIC HEALTH BOSTON MA
|
| Accumulating evidence points to a role of chronic inflammation in the pathogenesis and progression of cancers, including prostate. Infections are important agents in the genesis of inflammation. For prostate cancer, several lines of evidence point to a role of infections as important agents, although no specific infection has consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis, the most ... |
|
| Cell Fusion as a Cause of Prostate Cancer Metastases |
Apr 2011 |
25 pages |
| Authors:
Yuri Lazebnik; COLD SPRING HARBOR LAB NY
|
| The main goal of the study funded by this grant was to test a hypothesis that cell fusion between tumor cells, or between tumor and normal cells, contributes to metastasis. This hypothesis suggests that cell fusion contributes to carcinogenesis through two mechanisms: by generating cells with diverse genetic and epigenetic properties and by providing tumor cells with qualities of normal cells that are required to travel throughout the body while ... |
|
| Using Human Stem Cells to Study the Role of the Stroma in the Initiation of Prostate Cancer |
MAR 2011 |
35 pages |
| Authors:
Gail Risbridger; MONASH UNIV CLAYTON (AUSTRALIA)
|
| This project aimed to determine the role of tumor stroma in prostate cancer biology. To do this, we used a model of human embryonic stem cell (hESC) differentiation that was established in our laboratory. Using hESC-derived prostatic epithelial cells, we attempted to determine whether or not tumor stroma derived from human prostate cancer specimens induce and initiate carcinogenesis. The data generated in this funded project failed to support the hypothesis ... |
|
| Role of Melanin in Oncogenesis |
28 FEB 2011 |
13 pages |
| Authors:
Vashisht G. Yennu-Nanda; TEXAS UNIV SMITHVILLE MD ANDERSON CANCER CENTER
|
| Increased solar radiation and other unknown factors induce excess melanin production in melanocytes accumulated in localized areas of the skin, leading to formation of benign moles and infrequently, malignant moles that progress to melanoma. My hypothesis in the current research project is that excess melanin production in melanocytes may cause physico-chemical constraints on the metabolic activities of DNA and RNA, which, in rare instances, may induce pro-survival responses, including mutations, ... |
|
| The Role of Tim50 in Chemoresistance and Oncogenesis of Breast Cancer |
FEB 2011 |
15 pages |
| Authors:
Heidi Sankala; VIRGINIA COMMONWEALTH UNIV RICHMOND
|
| To investigate how gain of function p53 mutants exert their oncogenic effects, protein expression was compared between a p53 null cell line stably expressing vector alone or the p53 gain of function mutants, p53-R175H and -R273H. One protein that was upregulated in cells expressing the p53 gain of function mutants control cell lines was identified by mass spectrometry as translocator of the mitochondrial membrane 50 (Tim50). p53-R175H and -R273H, but ... |
|
| Hsf1 in Her2-positive Breast Cancer |
Feb 2011 |
10 pages |
| Authors:
Michael Sherman; BOSTON UNIV MEDICAL CAMPUS MA
|
| In the first year of the grant we addressed tasks 1, 2 and 3. Specifically we demonstrated that Hsf1 controls development of Her2-positive cancer both at the stage of initiation, where is affects the oncogene-induced senescence, and later at the stage of progression, where it affects tumor angiogenesis. We also dissected the mechanism of effects of Hsf1 on tumor angiogenesis, and demonstrated that Hsf1 regulates expression of the major angiogenesis ... |
|
| The Carcinogenic Potential of JP-8 and Tungsten in C57BL/6 Mice |
31 JAN 2011 |
40 pages |
| Authors:
Robert C. Lantz; ARIZONA UNIV TUCSON
|
| Little of the etiology of childhood leukemia is known; evidence indicates that childhood leukemia is a genetic disease originating in utero. Because of the probable multi-factor etiology of leukemia, multi-exposure investigations will contribute more useful information than conducting only single exposure studies. The combination of two environmental exposures, jet propellant-8 (JP-8) and tungsten (W), is unique to military personnel and their families. In the current study, we have used an ... |
|
| Fibroblast TGF-beta Signaling in Breast Development and Cancer |
SEP 2010 |
14 pages |
| Authors:
Aubie Shaw; VANDERBILT UNIV NASHVILLE TN
|
| Hypothesis: This proposal will address the hypothesis that TGFbeta signals in fibroblasts allow normal mammary gland development; and prevents breast cancer growth and progression. Specific Aims: We will (1) determine the effect of loss of TGFbeta signaling within stromal cells on mammary gland development and (2) determine the effect of loss of TGFbeta signaling within stromal cells on mammary carcinoma development. Study Design: This will be accomplished using transgenic mice ... |
|
| Modulation of Stat3 Alternative Splicing in Breast Cancer |
Sep 2010 |
27 pages |
| Authors:
Luca Cartegni; SLOAN-KETTERING INST FOR CANCER RESEARCH NEW YORK
|
| Stat3 is a transcription factor constitutively active in a large number of breast cancers and other tumors, where it works as a central player in the activation of multiple oncogenic pathways. We developed a method to modulate endogenous Stat3 alternative splicing using modified antisense oligonucleotides, to induce the dominant negative Stat3-beta variant in vitro and in vivo. Switching from the full length Stat3 isoform to the stat3-beta variant leads to ... |
|
| The Role of eIF4E Activity in Breast Cancer |
AUG 2010 |
20 pages |
| Authors:
James N. McElwaine; CAMBRIDGE UNIV (UNITED KINGDOM)
|
| Increased expression of eIF4E has frequently been reported in breast cancers and is thought to make fundamental contributions to disease development and progression. Increased eIF4E activity acts to enhance the translation of oncogenic cancer-related transcripts that contain highly structured 5' untranslated regions (UTRs) in their mRNAs. Over-expression of eIF4E has been shown to correlate with poor prognosis in breast cancer therefore the level of eIF4E over-expression has been studied extensively ... |
|
| Deregulation of miRNAs Contributes to Development and Progression of Prostate Cancer |
AUG 2010 |
10 pages |
| Authors:
Ralph W. deVere White; CALIFORNIA UNIV DAVIS
|
| The overall hypothesis of our proposal is that miR-125b acts as an oncogene, contributing to the development and progression of prostate cancer. In this grant, we proposed to test the ability of aberrantly-expressed miR-125b to promote tumorigenesis and to induce AI growth in three specific aims. In the first year, our focusThe overall hypothesis of our proposal is that miR-125b acts as an oncogene, contributing to the development and progression ... |
|
| Exploitation of Nontraditional Crop, Yacon, in Breast Cancer Prevention Using Preclinical Rat Model |
JUL 2010 |
18 pages |
| Authors:
Weiqin Jiang; Zongjian Zhu; COLORADO STATE UNIV FORT COLLINS
|
| Yacon has recently been introduced into farmer's markets and natural food stores in the US, but its preventive activity for breast cancer has rarely been evaluated. Objective are to determine the effect of dietary yacon on 1-methyl-1-nitrosourea (MNU) induced mammary carcinogenesis in rat; to evaluate the circulating factors and their association with the carcinogenesis; and to determine cellular signaling pathways ? HDAC and downstream targets - AMPK/Akt-mTOR and ghrelin-IGF1 axis. ... |
|
| Testing the Oncogenic Relevance of Cell Adhesion and Cytosketal Genes Affected by DNA Deletions in Breast Cancer |
JUL 2010 |
35 pages |
| Authors:
Scott Powers; COLD SPRING HARBOR LAB NY
|
| There are numerous genomic alterations that occur in breast cancer and most other commonly occurring epithelial cancers, but we still don't have a complete understanding of which of the hundreds of altered genes are actually doing something to cause or maintain cancer progression. It is important to have a complete understanding so that we can design more effective therapies. In this project we have used functional assays to test the ... |
|
| Targeting IKK in Basal-Like Breast Tumors as a Therapeutic Approach |
JUN 2010 |
20 pages |
| Authors:
Albert S. Baldwin; NORTH CAROLINA UNIV AT CHAPEL HILL
|
| Specifically, our hypothesis is that IKK and a form of NF-kappa B are activated in certain breast tumors (including the majority of basal-like tumors and in Her2+ cancers), leading to the expression of genes which promote oncogenesis and which lead to resistance to therapy. Additionally, we hypothesize that these tumors will respond to inhibitors of this pathway, either alone or in combination with chemotherapy. Based on our findings, we hypothesize ... |
|
| RNA Binding Proteins Posttranscriptionally Regulate Genes Involved In Oncogenesis |
JUN 2010 |
42 pages |
| Authors:
Ulus Atasoy; J. W. Davis; Tim Hoffman; MISSOURI UNIV-COLUMBIA
|
| Whereas transcriptional gene regulation is well studied, posttranscriptional gene control is poorly understood. Yet, emerging evidence indicates that posttranscriptional control by RNA binding proteins (RBPs) and microRNAs (miRNAs) are important key regulators of gene expression of many cancer related genes. The RBP, HuR, is a master regulator of many early response genes in cancer. Of the six classical acquired traits first proposed by Hanahan and Weinberg that malignantly transformed cells ... |
|
| HER2 Oncogene-Induced DNA Damage Response as a Barrier that Must Be Overcome to Form Breast Tumors In Normal Mammary Epithelium |
Mar 2010 |
18 pages |
| Authors:
Yi Li; BAYLOR COLL OF MEDICINE HOUSTON TX
|
| Activated ErbB2 stimulates mammary cell proliferation in culture and in mice; yet it is not sufficient by itself to cause mammary tumors when tested in mice. Oncogene-induced over-proliferation (but not high proliferation associated with normal development) has been reported to induce a DNA damage response (DDR), leading to apoptosis and senescence, but it is not known whether this response may be what prevents breast cancer initiation in cells that have ... |
|
| The Role of eIF4E Activity in Breast Cancer |
Aug-2009 |
12 pages |
| Authors:
Thomas A Hughes; L A Coleman; S Satheesha; LEEDS UNIV (UNITED KINGDOM)
|
| Increased eIF4E expression occurs in many breast cancers and makes fundamental contributions to carcinogenesis by stimulating expression of cancer-related genes at post-transcriptional levels. This key role is highlighted by the facts that eIF4E levels can predict prognosis and that eIF4E is an established therapeutic target. However, eIF4E activity is a complex function of expression levels and phosphorylation statuses of eIF4E and its regulatory proteins. Our hypothesis was that combined analyses ... |
|
| Mechanisms Underlying the Breast Cancer Susceptibility Locus Mcs5a |
Jul-2009 |
15 pages |
| Authors:
Bart M Smits; WISCONSIN UNIV-MADISON
|
| For low-penetrance breast cancer risk alleles it is currently unknown how they lead to predisposition. Here, we study the Mcs5a locus that is associated with breast cancer risk in rats and humans. In our rat model we show that the presence of the resistant genotype of two components of the locus (Mcs5a1, Mcs5a2) down regulates the expression of the Fbxo10 gene in the T cells and that this reduced expression ... |
|
| Genomic Approaches for Detection and Treatment of Breast Cancer |
Jul-2009 |
28 pages |
| Authors:
Stephen J Elledge; BRIGHAM AND WOMEN'S HOSPITAL BOSTON MA
|
| The experiments carried out under this Innovator award allowed us to set up a genetic system to identify genes through loss of function (RNAi) or gain of function (over-expression) functional screens that are capable of influencing cells to acquire tumorlike properties. In this way we have identified many novel tumor suppressors and oncogenes. Many of these are found to be altered in breast cancer and other cancer types. Importantly, we ... |
|
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