Molecular study of sex steroid receptor gene expression in human colon and in colorectal carcinomas.

Abstract

Sex steroid hormones influence function of the human gastrointestinal tract. Although the specific receptor proteins have been identified in surgical specimens of both intestinal mucosa and colorectal carcinomas, it is still unknown whether they are expressed in intestinal epithelial cells. Expression of androgen receptor (AR) protein and estrogen receptor (ER) protein was studied by Scatchard analysis and ELISA (for ER only) in surgical specimens of normal-appearing mucosa, colorectal carcinomas, isolated colonocytes, and human colorectal carcinoma cell lines. Northern analysis was applied to identify the appropriate mRNAs, followed by the sensitive technique of reverse transcription-polymerase-chain-reaction (RT-PCR). AR protein was identified in all surgical specimens analyzed and ER protein in 10 out of 13 normal-appearing mucosa specimens and 4 out of 7 colorectal carcinomas. The receptor proteins were not found in isolated colonocytes or in the transformed cell lines. RT-PCR confirmed that none of the isolated normal colonocytes or transformed colorectal carcinoma-derived cells expressed these mRNAs. Intestinal smooth muscle cells and fibroblasts were found to express sex steroid receptor mRNAs. Both receptors are present in human large intestine but are expressed in stromal cells and not in intestinal epithelial cells. We hypothesize that sex steroids may influence the function of colonocytes indirectly through stromal-epithelial interactions.