| Mechanisms of KAI1/CD82-Induced Prostate Cancer Metastasis |
Aug 2011 |
40 pages |
| Authors:
Cynthia Miranti; VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI
|
 | Metastatic prostate cancer kills over 28,000 American men every year. The mechanisms that drive metastasis are poorly understood. We investigated the hypothesis that loss of the metastasis suppressor gene, CD82/KAI1 in primary prostate tumors of genetically engineered mice would be sufficient to induce metastasis. While CD82 was sufficient to suppress metastasis of metastatic tumor cells lines and did so by repressing c-Met, the reverse was not true, i.e. loss of ... |
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| Role of Integrin-Beta 1 in Polycystic Kidney Disease |
Apr 2011 |
25 pages |
| Authors:
Gabriele L Gusella; MOUNT SINAI SCHOOL OF MEDICINE NEW YORK
|
| Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the dysregulation of the PKD1 or PKD2 genes. Among the multiple molecular and biological changes associated with the cystogenic conversion are the amplification of the centrosome, genomic instability and aneuploidy, as well as an increase in the expression of the adhesion molecule integrin!1. The scope of the study is to elucidate in the molecular mechanism underlying these events and the role ... |
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| Defining the Role of Integrin Alpha 11 in Wound Healing and Fibrosis |
SEP 2010 |
27 pages |
| Authors:
Ruth M. Baxter; SYNEDGEN INC CLAREMONT CA
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| Integrin alpha 11 (Itga11) is the most recently identified integrin subunit and has been associated with fibrotic disease. To investigate the role of Itga11 in fibroblast behavior in wound healing and fibrosis we used Itga11 null mice. We have found that fibroblasts lacking Itga11 (KO) repair a scratch in a confluent monolayer faster than their normal (Het) counterparts, and show increased proliferation along the margins of the scratch. In an ... |
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| A Role for MEK-Interacting Protein 1 in Hormone Responsiveness of ER Positive Breast Cancer Cells |
01 JUL 2010 |
14 pages |
| Authors:
Susan E. Conrad; MICHIGAN STATE UNIV EAST LANSING
|
| We have identified a novel role for the small scaffold protein MP1 in the survival of ER-positive breast cancer cell lines. Blocking MP1 expression using siRNA leads to apoptotic cell death in ER-positive MCF-7, LCC9 and T47D cells, but not in ER-negative MDA-MB-231, SKBr3 and BT-549 cell, or in non-tumorigenic 184B5 cells. Inhibition of MP1 expression in MCF-7 cells resulted in decreased ER expression and activity, and decreased AKT phosphorylation. ... |
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| Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent |
Apr-2009 |
7 pages |
| Authors:
Francis S Markland; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Ovarian cancer (OC) is the deadliest of all gynecological cancers, with five year survival rates of 45%. One critical feature of the disease is that two-thirds of the women diagnosed have advanced disease, and the five year survival rate of this group is 30%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and diagnostic ... |
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| Phospholipase C gamma 1: Mechanisms of Adhesion and Role in Migration and Metastasis |
Mar-2009 |
39 pages |
| Authors:
Cornelia Crooke; VANDERBILT UNIV NASHVILLE TN
|
| Phospholipase C-gamma1 (PLC-gamma1) mediates cell adhesion and migration through an undefined mechanism. Here, we examine the role of PLC-gamma1 in cell-matrix adhesion in a hanging drop assay of cell aggregation. Plcg1 Null (-/-) mouse embryonic fibroblasts formed aggregates that were larger and significantly more resistant to dissociation than cells in which PLC-gamma1 is re-expressed (Null + cells). Aggregate formation could be disrupted by inhibition of fibronectin interaction with integrins, indicating ... |
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| Mechanisms of KAI1/CD82 - Induced Prostate Cancer Metastasis |
Feb-2009 |
28 pages |
| Authors:
Cynthia Miranti; VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI
|
| Our basic understanding of how prostate cancer metastasis develops is limited. The recent identification of genes, whose expression suppresses metastasis but not growth in xenograft models, has provided a potential avenue for better understanding the metastatic process. The overall objective of this proposal is to determine how loss of the metastasis suppressor, KAI1/CD82, promotes the development of metastatic prostate cancer. Elevated expression of integrins a6b1 and a3b1 is highly correlative ... |
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| Identification of Molecular Receptors for Therapeutic Targeting in Prostate Cancer |
Dec-2008 |
15 pages |
| Authors:
Paul J Mintz; IMPERIAL COLL LONDON (UNITED KINGDOM)
|
| Prostate cancer is a difficult disease to treat due to its molecular heterogeneity and diverse clinical outcomes. Current therapies for treating and diagnosing prostate cancer are unsatisfactory, suggesting that new strategies and molecular markers are greatly needed. Tumor cells express specific cell surface receptor complexes for rapid growth and survival. Specific receptor-ligand complexes have profound biological functions such as cell signaling and growth. For example, androgen receptor complex plays a ... |
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| Development of a Multifaceted Ovarian Cancer Therapeutic and Imaging Agent |
01-Apr-2008 |
11 pages |
| Authors:
Francis S Markland; UNIVERSITY OF SOUTHERN CALIFORNIA LOS ANGELES
|
| Ovarian cancer (OC) is the deadliest of all gynecological cancers, with five year survival rates of <45%. One critical feature of the disease is that two thirds of the women diagnosed have advanced disease, and the five year survival rate of this group is <30%. This project outlines the development of a recombinant version of a member of a class of proteins known as disintegrins as an innovative imaging and ... |
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| Integrin-Mediated Signaling in Prostate Cancer: Role of KAI1/CD82 in Regulating Integrin and Androgen Receptor Function During Metastasis |
SEP 2007 |
64 pages |
| Authors:
Cynthia K. Miranti; VAN ANDEL RESEARCH INSTITUTE GRAND RAPIDS MI
|
| How prostate tumors become metastatic is virtually unknown. A prostate metastasis suppressor gene, KAI1/CD82, known to associate with laminin receptors, allowed us to test the hypothesis that loss of KAI1/CD82 expression alters the function of laminin integrins in prostate cancer cells, resulting in altered intracellular signaling and increased invasion leading to metastasis. We have demonstrated that in metastatic tumor cells, where elevated c-Met expression and activation by integrins is responsible ... |
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| Ultrasound Imaging of Breast Cancer |
JUL 2007 |
6 pages |
| Authors:
Paul W. Erhardt; TOLEDO UNIV OH
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| The synthesis of the fully-protected version of the target probe compound (i.e. its penultimate intermediate) has been accomplished on a scale that should be large enough to yield the desired amount of the final product. Attempts to develop an in vitro, cell culture assay for enhancement of ultrasound images have not yet been successful. |
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| Targeting of CD151 in Breast Cancer and in Breast Cancer Stem Cells |
01-Apr-2007 |
34 pages |
| Authors:
Martin E Hemler; DANA-FARBER CANCER INST BOSTON MA
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| A mouse model for spontaneous breast cancer has been set up to analyze the role of CD151 during breast cancer progression. Using this model, which involves amplification of the ErbB2 oncogene, preliminary data was then obtained indicating that the absence of CD151 causes a substantial delay in the appearance of mouse mammary tumors. To confirm these preliminary results, we next set up a larger scale experiment to evaluate the role ... |
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| Adhesion-Linked Protein Tyrosine Phosphatases, Morphogenesis and Breast Cancer Progression |
JUL 2006 |
21 pages |
| Authors:
Valerie M. Weaver; PENNSYLVANIA UNIV PHILADELPHIA
|
| Stromal-epithelial interactions regulate breast cell fate via integrin-growth factor receptor (GFR) interactions that activate tyrosine kinases that are tempered by protein tyrosine phosphatases (PTP). Using a series of molecular screening approaches we profiled PTP expression in normal transformed and phenotypically-reverted breast tissue and identified the Band 4.1 PTPs MEGI and D1 as candidate PTP metastasis suppressors. Our studies have implicated two Band 4.1 PTPs MEGI and D1 as important regulators ... |
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| Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene |
MAY 2006 |
121 pages |
| Authors:
David H. Gorski; ROBERT WOOD JOHNSON MEDICAL SCHOOL PISCATAWAY NJ
|
| Homeobox genes represent a class of transcription factors important in embryogenesis, organogenesis cell growth and differentiafion and cell migration. However there is little known about their role in regulating endothelial cell (EC) phenotype in response to proangiogenic factors secreted by breast cancer although at least two homeobox genes have been implicated in inducing the angiogenic phenotype in ECs. We are therefore testing the homeobox gene Gax regulates breast cancer-induced angiogenesis ... |
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| Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene |
MAY 2005 |
60 pages |
| Authors:
David H. Gorski; UNIVERSITY OF MEDICINE AND DENTISTRY OFNEW JERSEY PISCATAWAY
|
| Homeobox genes represent a class of transcription factors important in embryogenesis, organogenesis, cell growth and differentiation, and cell migration. However, there is little known about their role in regulating endothelial cell (EC) phenotype in response to proangiogenic factors secreted by breast cancer, although at least two homeobox genes have been implicated in inducing the angiogenic phenotype in ECs. We are therefore testing the homeobox gene Gax regulates breast cancer-induced angiogenesis ... |
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| Rho GTPase Involvement in Breast Cancer Migration and Invasion |
MAR 2005 |
23 pages |
| Authors:
Kaylene J. Simpson; BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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| The RhoGTPases play a critical role in cell migration via regulation of cytoskeletal changes. Increased expression of Rho proteins. in particular RhoC, have been associated with invasive carcinoma, however, the functional contributions of the individual isoforms have been difficult to evaluate due to insufficient molecular tools. We used a stable retroviral RNAi approach to abrogate expression of RhoA or RhoC in the SUM-159 invasive breast carcinoma cell line. We observed ... |
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| Integrin-dependent Antagonism of Tamoxifen Therapy through Transcriptional Replacement: Establishing a Basis for a New Combined Therapy |
AUG 2004 |
13 pages |
| Authors:
Erica A. Golemis; INSTITUTE FOR CANCER RESEARCH PHILADELPHIA PA
|
| Accruing evidence suggests that integrin-dependent cell attachment signaling, and estrogen hormonal response are closely interconnected. For example, studies by us and others of the BCAR proteins (BCAR1 and BCAR3: (1, 2)) have indicated that these proteins physically associate with each other, and function both in signal transduction relevant to integrin stimulation, and in mediation of Tamoxifen (Tam) resistance. The goal of this proposal was to explore the interrelationship between integrin ... |
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| Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene |
MAY 2004 |
91 pages |
| Authors:
David H. Gorski; UNIVERSITY OF MEDICINE AND DENTISTRY OFNEW JERSEY NEW BRUNSWICK
|
| Homeobox genes represent a class of transcription factors important in embryogenesis, organogenesis, cell growth and differentiation and cell migration. However, there is little known about their role in regulating endothelial cell (EC) phenotype in response to proangiogenic factors secreted by breast cancer, although at least two homeobox genes have been implicated in inducing the angiogenic phenotype in ECs. We are therefore testing the homeobox gene Gax regulates breast cancer-induced angiogenesis ... |
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| Sulfur Mustard Disrupts Human Alpha(3)Beta(4)-Integrin Receptors in Concert With Alpha(6)Beta(4)-Integrin Receptors and Collapse of the Keratin K5/K14 Cytoskeleton |
2004 |
11 pages |
| Authors:
Robert J. Werrlein; Catherine R. Braue; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
|
| Sulfur mustard (SM; bis(2-chloroethyl) sulfide) is a chemical warfare agent that produces persistent, incapacitating blisters of the skin. The lesions inducing vesication remain elusive, and there is no completely effective treatment. Using multiphoton microscopy and immunofluorescent staining, we found that exposing human epidermal keratinocytes (HEK) and intact epidermis to SM (400 muM for 5 min) caused progressive collapse of the keratin (K5/K14) cytoskeleton and depletion of alpha6beta4 integrins.1 We now ... |
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| Neoadjuvant Anti-Angiogenesis Therapy for Prostate Cancer |
AUG 2003 |
7 pages |
| Authors:
Mitchell H. Sokoloff; CHICAGO UNIV IL MEDICAL SCHOOL
|
| This protocol is designed to evaluate the effects of combined anti- angiogenesis and androgen ablation therapy in men at high risk for recurrence after radical prostatectomy. Both clinical (i.e., pathologic, disease-free survival, safety) and molecular factors will be evaluated. A clinical trial to test the effectiveness of this therapy was initiated in January 2003. After a slow initial accrual recruitment has been increasing steadily. It is still too early to ... |
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| Insulin-Like Growth Factor Binding Protein-1 Interacts with Integrins to Inhibit Insulin-Like Growth Factor-Induced Breast Cancer Growth and Migration |
JUL 2003 |
18 pages |
| Authors:
Jennifer M. Gross; MINNESOTA UNIV MINNEAPOLIS
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| The insulin-like growth factor (IGF) system and extracellular matrix proteins are key regulators of the malignant breast cancer phenotype. Both IGFs and extracellular matrix proteins communicate wit epithelial cells by ligating cell surface receptors. Therefore, ligand-receptor interactions of the two systems are relevant treatment targets in breast cancer cell growth. Studies have shown that IGFBP-l can bind to IGF and prevent IGF from interacting with its receptor and inhibit breast ... |
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