ANDROGEN INDUCES ORNITHINE DECARBOXYLASE GENE-EXPRESSION IN COLONIC CELL-LINE HT-29

Carcinoma of the colon is the second most common cancer among men and women combined in the United States. PURPOSE: Ornithine decarboxylase (ODC) is the first and key regulatory enzyme in the polyamine biosynth esis pathway and is regulated by various factors, Polyamines are belie ved 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 vi vo 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 c ell lines, SW620, HT-29, and Caco-2. METHODS: Cell lines were maintain ed in Dulbecco's Modified Eagle's medium/F12 supplemented with 5 perce nt fetal bovine serum. At GO percent confluency, medium was replaced w ith steroid-depleted medium, and incubation continued for 24 hours. Fo llowing this period, medium was replaced with fresh steroid-free mediu m containing 1 nM dihydrotestosterone. RESULTS: Dihydrotestosterone st imulated ODC messenger ribonucleic acid expression only in HT-29 colon ic cell line. Studies using electrophoretic mobility shift assays of n uclear extracts also showed a binding pattern with SP1 and NF-kappa B regulatory sequences only in testosterone-treated HT-29 cells. Conclus ion: These results suggest that androgens may play an important role i n the growth of HT-29 colonic cell lines.