Epidemiological studies of postmenopausal hormone replacement therapy show a reduction in the risk of developing colon cancer, and animal studies using 17β-oestradiol (E2) demonstrate a decreased incidence of chemically-induced colon cancer. Using the colon cancer cell line, COLO205, we found that E2 induced a dose-dependent increase in DNA fragmentation and nuclear condensation, significant effects being seen at 10 12 mol/l. BSA-conjugated E2, which cannot enter cells, was ineffective at inducing apoptosis in COLO205 cells, indicating that E2 was not acting through a cell-membrane receptor. E2 did not induce the morphological changes characteristic of differentiation.

Using RT-PCR we found that the oestrogen receptor α (ERα) isoform was absent in the COLO205 cell line in contrast to CACO-2, LoVo and SW620 cells, but mRNAs for ERβ1,-β2,-β5 and-β6 isoforms were detected. Western immunoblotting results showed fulllength ERβ protein but no detectable ERα in COLO205 cells. In normal human colon tissue samples immunoreactive ERβ was found but ERα was barely detectable. Expression of ERβ was lost in some colon cancer specimens and reduced in others. We conclude that E2, through ERβ, at concentrations found during replacement therapy, may inhibit the development of colon cancer by inducing apoptosis.