Alternately spliced luteinizing hormone/human chorionic gonadotropin receptor mRNA in human breast epithelial cells

Abstract

Luteinizing hormone (LH)/human chorionic gonadotropin (hCG) bind to a common transmembrane glycoprotein receptor, which is a member of the G protein-coupled receptor family. In human, the LH/hCG receptor gene is composed of 11 exons and 10 introns and its coding region is over 60 kb long. Human chorionic gonadotropin is a glycoprotein hormone containing a cystine-knot folding motif that is found in peptide growth factors known to activate the expression of homeogenes. In the present work we present evidence that hCG down-regulates all the three transcripts of HOXA1 at early stages of hCG treatment in the immortalized human breast epithelial cells (MCF-10F), whereas HOXA1-S1, the largest transcript, as well as HOXA1-S3, the smallest transcript, were up-regulated in the cancer cell lines MDA-MB-231 and MCF-7, respectively. This divergent reaction of hCG was associated with the pattern of LH/hCG receptors and splicing forms expression in human breast epithelial cells. MCF-10F cells expressed the full-length (1191 bp) compared with the cancer-derived cells MCF-7 and MDA-MB-231 that was weakly or not expressed. Isoform 1 (1117 bp) was silent in MCF-10F and expressed weakly in the cancer cells. The isoforms 2 (1006 bp) and 3 (932 bp) of LH/hCG gene receptor were silent in all the cell lines, whereas isoforms 4 (892 bp), 6 (626 bp) and 7 (441 bp) were silent in MCF-10F cells and expressed in the cancer cell lines. Instead isoform 5 (707 bp) showed in the three cell lines the strongest expression in MCF-10F cells. This difference in the expression of alternate splicing of LH/hCG receptor mRNA among the MCF-10F, MCF-7 and MDA-MB-231 cells, may explain the divergent response of these cells to HOXA1 activation by hCG.