Therapeutic Implications of Progesterone Receptor-Mediated Regulation of Cell Cycle in Breast Cancer
Abstract
Our studies show that agonist-bound PR-B can stimulate the proliferation of breast cancer cells by functioning in a direct manner to induce transcription of E2F1 and E2F2, key regulators of cell cycle progression. We demonstrate that although the MAPK pathway is important for phosphorylation of RB and release of E2F, its activation is not dependent on PR signaling through Src family kinases. Further, we found that PRMs such as asoprisnil that do not induce classic PR target genes can activate E2F signaling and stimulate proliferation. Future studies will explore this novel mechanism by which PR regulates breast cancer proliferation so that we can better enable development of PRMs that effectively inhibit breast tumor growth.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2007
- Accession Number
- ADA475543
Entities
People
- Hilary Ogden
Organizations
- Duke University