Androgen induces ornithine decarboxylase gene expression in colonic cell line HT-29.

Abstract

Carcinoma of the colon is the second most common cancer among men and women combined in the United States. Ornithine decarboxylase (ODC) is the first and key regulatory enzyme in the polyamine biosynthesis pathway and is regulated by various factors. Polyamines are believed to participate in cellular proliferation and differentiation. High levels of polyamines and ODC activity are associated with rapid cell growth, particularly in tumor tissues. Regulation of this enzyme in vivo has important clinical implications. In the present study, we used Northern analysis and mobility shift assay to investigate whether ODC gene expression is regulated by androgens in the three human colonic cell lines, SW620, HT-29, and Caco-2. Cell lines were maintained in Dulbecco's Modified Eagle's medium/F12 supplemented with 5 percent fetal bovine serum. At 60 percent confluency, medium was replaced with steroid-depleted medium, and incubation continued for 24 hours. Following this period, medium was replaced with fresh steroid-free medium containing 1 nM dihydrotestosterone. Dihydrotestosterone stimulated ODC messenger ribonucleic acid expression only in HT-29 colonic cell line. Studies using electrophoretic mobility shift assays of nuclear extracts also showed a binding pattern with SP1 and NF-kappaB regulatory sequences only in testosterone-treated HT-29 cells. These results suggest that androgens may play an important role in the growth of HT-29 colonic cell lines.