I.3 An epigenetic mechanism for tamoxifen-associated uterine carcinogenesis?

Tamoxifen is a potent anti-oestrogenic drug effective in treating human breast cancer but is associated with an increase in endometrial tumours in some women. Although tamoxifen is an oestrogen antagonist in the breast it possesses partial agonist activity in the human uterus. We hypothesise that tamoxifen's carcinogenic activity in the endometrium involves dysregulation of the transforming growth factor-beta (TGFβ) activation and signalling pathway. Consequently, we are screening human biopsies for alterations in these TGFβ pathways. Altered responsiveness to TGFβ signalling could form the basis of an epigenetic mechanism for endometrial carcinogenesis with tamoxifen.