Expression of estrogen receptor (ER) subtypes and ERβ isoforms in colon cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 61; no. 2; pp. 632 - 640
• Main Authors: CAMPBELL-THOMPSON, Martha, LYNCH, I. Jeanette, BHARDWAJ, Bhavna
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.01.2001
• Subjects: Biological and medical sciences; estrogen receptor ^b; Gastroenterology. Liver. Pancreas. Abdomen; Medical sciences; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; Molecular form; Gene product; Tumoral tissue; Estrogen; Malignant tumor; Gene expression; Carcinogenesis; In vitro; Colonic disease; Messenger RNA; Established cell line; Digestive diseases; Intestinal disease; Colon; Subtype; Tumor cell; Hormonal receptor
• ISSN: 0008-5472; 1538-7445

Colon cancer incidence and mortality rates are lower in females compared with males, and numerous epidemiological studies suggest that estrogen replacement therapy (ERT) reduces cancer risk in postmenopausal women. Two estrogen receptor (ER) subtypes, ER alpha and ER beta , mediate genomic effects in target cells. The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ER beta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines. ER alpha and ER beta isoform mRNA levels were investigated in paired samples of colon tumors and normal mucosa from 26 patients using comparative reverse transcription-PCR and then Southern analyses. Constitutive steroid hormone receptor mRNA levels were determined for five colon adenocarcinoma cell lines using reverse transcription-PCR, and ER beta levels were further studied in Caco-2 cells using Northern and Western analyses. ER beta mRNA steady-state levels (relative to glyceraldehyde-3-phosphate dehydrogenase mRNA) were significantly decreased in colon tumors compared with normal mucosa in female patients. ER beta 1 and ER beta 2 isoform mRNA levels were significantly decreased in tumors from female patients, and ER beta 1 mRNA levels were also significantly lower in tumors from female patients compared with tumors from males. ER alpha mRNA levels were much lower than ER beta levels and were similar between normal mucosa and tumor samples in both genders. ER beta mRNA was detected in Caco-2, T84, and SW1116 cell lines and all lines were essentially negative for ER alpha mRNA. Caco-2 cells coexpressed ER beta 1, ER beta 2, and ER beta 5 mRNA, though a single protein transcript was observed. ER beta protein was detected in normal colonic superficial epithelium, vascular smooth muscle and endothelium, and enteric neurons by immunohistochemistry. These data show that ER beta is the predominant ER subtype in the human colon and that decreased levels of ER beta 1 and ER beta 2 mRNA are associated with colonic tumorigenesis in females. This information suggests that activation of ER beta -mediated processes in the superficial colonic epithelium may have a role in the preventive effects observed for female gender and ERT usage.