Endocrine Abstracts

Epidemiological studies of postmenopausal women on oral oestrogen replacement therapy (ERT) show a reduction in the risk of developing colon carcinoma. Our previous study demonstrated that 17beta-oestradiol (E2) induced apoptosis in COLO205, a colonic cancer cell line. The aim of this study is to identify the genes important in the E2-induced apoptosis. cDNA array analysis 24h post E2 treatment showed a decrease in mRNA of erbB3 of 92%, K-RAS of 83% and p68TRK-T3 of 98% whereas GADD153 (growth arrest and DNA damage-inducible protein 153) was increased 532%, compared with control. Western blotting confirmed a dose-dependent GADD153 upregulation which disappeared at 48h and a reduction in the expression of K-RAS with E2 for 24 h. DNA sequencing showed a mutation in K-RAS in COLO205 cells with single nucleotide insertion. Butyrate which also induced apoptosis in these cells did not regulate GADD 153 or K-RAS suggesting the mechanisms to induce apoptosis differ in the 2 pathways. In summary, upregulation of GADD153 and downregulation of K-RAS may be involved in E2-induced apoptosis in COLO205 cells.