Progesterone Regulation of Insulin Receptor Substrates Mediates Focal Adhesion Formation in Breast Cancer Cells
Abstract
How progesterone and IGF signaling pathways cross-talk with each other to regulate breast cancer progression remains a critical question. In this study, it was found that progesterone enhances IGF-induced cell motility using PR-B-transfected C4-12 cells. To assess whether the progesterone effect is via regulation of IRS-l/2 expression and activation, I performed RT-PCR and western blot analysis. It was found that IRS-2 was sharply up-regulated by progestins through transcriptional mechanisms in MCF-7, T47D, ZR75, and especially in PR-B C4-12 cells while IRS- 1 was not. This indicates that IRS-1 and IRS-2 are distinctively regulated by progestins. Moreover, IRS-2 and its downstream signaling elicited by IGF-I were enhanced by progesterone, which was shown by immunoprecipitation. These data, together with previous findings that IRS-2 is activated by integrins, provide a clue that IRS-2 may be involved in progestin increase of IGF-induced cell motility.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2003
- Accession Number
- ADA418730
Entities
People
- Adrian Lee
- Xiaojang Cui
Organizations
- Baylor University