Progesterone Regulation of Insulin Receptor Substrates Mediates Focal Adhesion Formation in Breast Cancer Cells
Abstract
To test our hypothesis that progesterone induces focal adhesion in breast cancer cells through its regulation of IRS-1/2 expression and activation, I first determined whether progesterone regulated focal adhesion in different breast cancer cell lines with distinct progesterone receptor (PR) and insulin receptor substrate (IRS)-1/2 levels preliminary analysis using Texas-red-phalloidin and fluorescence microscopy showed that stress formation was induced in PR-B transfected C4-12 cells (ER-/PR-MCF-7 sublines). To assess whether progestins induce cell adhesion through regulation of IRS-1/2 expression and activation, I performed RT-PCR and western blot analysis. It was found that IRS-2 was sharply up-regulated by progestins in MCF-7, T47D, and especially in PR-B C4-12 cells while IRS-1 was only slightly induced. This indicates that IRS-1 and IRS-2 are distinctively regulated by progestins. Co-treatment of R5020 with the transcription inhibitor 5,6-dichlorobenzimidazole riboside(DRB) blocked the induction of IRS-2, suggesting that the progestin effect was mediated by a transcriptional mechanism. These data provide a clue that IRS-2 may be involved in progestin-induced cell adhesion as IRSs have been shown to interact with many cell adhesion proteins.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA415598
Entities
People
- Adrian Lee
- Xiaojiang Cui
Organizations
- Baylor College of Medicine