Homobox Genes Mediates the Biological Functions of Human Chorionic Gonadotropin (hCG) in Human Breast Epithelial Cells

摘要

Our study shows that 33 out of the 39 cluster I homeobox genes are expressed in the immortalized human breast epithelial cells MCF-10F, 35 in breast cancer ER-positive cells MCF-7 and 36 in breast cancer ER-negative cells MDA-MB-23l. In MCF-l0F cells, recombinant human chorionic gonadotropin (r-hCG) rapidly down-regulated all the three transcripts of HOXAl (HOXAl-S1, S2 and -S3) at 1- and 5-hour points, and transiently induced expression of HOXA2, the silent gene, at very early stage. In addition, exogenous r-hCG could increase the expression levels of HOXD8, D10, Dll and D13 genes. In MCF-7 cells, r-hCC treatment resulted in up-regulation of HOXAl-S3, B3, B8 and Dll genes. In MDA- MB-231 cells, r-hCG treatment up-regulated the expression of HOXAl-S1, C8, D8 and Dli genes. A significant finding of this study is that hCG rapidly induces the transient expression of HOxA2, the silent gene in MCF-10F. We further demonstrated that HOXA2 is involved in the modulation of AP-l, since using EMSA we observed a higher level of AP-l activation by TNF were observed in MCF-10F cells. However, after transient transfection with HOXA2 cDNA expression construct, the AP-l biding activity was significantly decreased. Indicating that the effect of r-hCG on APi expression is modulated by HOX A2.