Accession Number:

ADA415598

Title:

Progesterone Regulation of Insulin Receptor Substrates Mediates Focal Adhesion Formation in Breast Cancer Cells

Descriptive Note:

Annual summary rept. 1 Jul 2001-30 Jun 2002

Corporate Author:

BAYLOR COLL OF MEDICINE HOUSTON TX

Personal Author(s):

Report Date:

2002-07-01

Pagination or Media Count:

6.0

Abstract:

To test our hypothesis that progesterone induces focal adhesion in breast cancer cells through its regulation of IRS-12 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-12 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-12 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 ribosideDRB 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.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE