Expression profile of agonistic Smads in human breast cancer cells: Absence of regulation by estrogens

✍ Scribed by Frederic Pouliot; Claude Labrie

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 153 KB
• Volume: 81
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990331)81:1<98::aid-ijc17>3.0.co;2-9

✦ Synopsis

Transforming growth factor-␤1 (TGF-␤1) is a cytokine expressed by mammary cells. While TGF-␤1 can inhibit the proliferation of human breast cancer cells, many cell lines are unresponsive to it. To shed light on the mechanisms underlying resistance to TGF-␤1, we examined expression of the mediators of TGF-␤1 signaling in the mammary carcinoma cell lines MCF-7, T47D, ZR-75-1, BT-20, MDA-MB-231 and MDA-MB-468. The levels of mRNA encoding Smad2, 3 and 4 as well as the type II (T␤RII) and type I (T␤RI) membrane receptors were determined by Northern analysis and/or ribonuclease protection assays. Smad2 and Smad3 mRNAs were detected in all 6 cell lines examined, whereas Smad4 mRNA was not detected in MDA-MB-468 cells, which are known to harbor a homozygous deletion of the Smad4 gene. T␤RI was expressed in all 6 cell lines, whereas T␤RII was not detected in ZR-75-1 and T47D cells. Of the cell lines tested, only MCF-7 cells were growth-inhibited by TGF-␤1. In contrast, only MDA-MB-231 cells showed induction of the PAI-1 promotor in response to TGF-␤1. We also examined the regulation of Smad mRNA expression by estrogens and androgens in ZR-75-1 cells. Neither estradiol nor dihydrotestosterone affected Smad2, 3 or 4 mRNA levels in ZR-75-1 cells. These results indicate that the lack of response to TGF-␤1 in the breast cancer cell lines examined can be attributed to the absence of either T␤RII or the Smad4 gene product. Moreover, we show that the proliferative and transcriptional responses to TGF-␤1 are dissociable and that Smad expression is not regulated by sex steroids in ZR-75-1 cells. Int.