tailieunhanh - Báo cáo Y học: Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells

A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A tran-script of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by prog-esterone and different progestins, but not by dihydrotestos-terone or dexamethasone, and which was abrogated by antiprogestin RU486 | Eur. J. Biochem. 269 2485-2490 2002 FEBS 2002 doi Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells Tytti M. Ahola1 Sami Purmonen1 Pasi Pennanen1 Ya-Hua Zhuang1 Pentti Tuohimaa3 and Timo Ylikomi1 2 1 Department of Cell Biology Medical School 33014 University of Tampere Finland department of Clinical Chemistry Tampere University Hospital Finland 3Department of Anatomy University of Tampere Finland A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate MPA . A transcript of G-protein-coupled receptor 30 GPR30 was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestinspecific primary target gene which was enhanced by progesterone and different progestins but not by dihydrotestosterone or dexamethasone and which was abrogated by antiprogestin RU486. The dose-dependent and timedependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1 ERK2 pathway is capable of inducing progesterone receptordependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation but the p38 pathway inhibitor induced GPR30 expression which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene the expression of which correlates with growth inhibition. Keywords breast cancer differential display G-protein-coupled receptor progestin proliferation. Progestins are widely used for therapeutic purposes such as contraception and hormonal replacement therapy. In the uterus they oppose the .