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Abstract:
One goal this research project has been to assess the dependence of breast cancer cell survival on the P13 kinase/Akt signaling pathway. This signaling pathway is hypothesized to be critical to breast cancer survival especially under growth-limiting conditions or when chemotherapeutics are present. Using a series of six breast cancer cell lines and a phenotypcially normal, but immortal, breast line I first determined the baseline level of phosphorylated Akt as an indicator of basal P13 kinase signaling. Phosphorylated ERKl/2 was also measured to determine if basal survival signaling through the MEKl/2-ERKl/2 pathway was occurring. While all of the breast cancer cell lines expressed basal levels of phosphorylated ERKl/2, phosphorylated Akt was only found in a fraction of the cell lines. The removal of exogenous growth factors by culture in serum-free media did not significantly change the detected level of phosphorylated Akt and ERKl/2 expressed by the cells, suggesting that P13 kinase-Akt and MEKl/2-ERKl/2 signaling occurs in the absence of exogenous growth factors. Pharmacological inhibitors of these key survival signaling pathways were tested for their affects on breast cancer cell survival under both serum- free and serum-containing conditions. Interestingly, the results to date suggest that most breast cancer cell lines rely more heavily on the MEKl/2-ERKl/2 signaling pathway than on the P13-kinase-Akt pathway for survival.
| Limitations: |
 APPROVED FOR PUBLIC RELEASE |
| Description: |
Annual summary rept. 1 May 2001-30 Apr 2002 |
| Pages: |
10 |
| Report Date: |
MAY 2002 |
| Contract Number: |
DAMD17-00-1-0222 |
| Report Number: |
A702704 |
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