ANTIESTROGEN STIMULATED HUMAN ENDOMETRIAL CANCER GROWTH - LABORATORY AND CLINICAL CONSIDERATIONS

The new antiestrogen toremifene (TOR) is currently on the market for t he treatment of advanced breast cancer in postmenopausal women. TOR is known to exhibit a similar efficacy profile as tamoxifen (TAM) in the treatment of advanced breast cancer and there are studies to suggest that the beneficial side effects of TAM. on bone and blood lipids are also achieved with TOR. However, the data concerning the action of TOR on the endometrium is sorely lacking. In light of the estrogenic effe ct of TAM on the uterus and the 2-3-fold increased incidence in endome trial carcinoma detected in patients receiving TAM therapy, it is impe rative to investigate the effect of TOR on endometrial carcinoma. We c ompared the actions of TAM and TOR on the EnCa101 human endometrial tu mor model and find that both antiestrogens have similar growth stimula tory effects. To investigate a potential mechanism of antiestrogen-sti mulated endometrial tumor growth, we have examined known activators of the AP-1 signal transduction pathway, the protein kinase C (PKC) fami ly of isozymes, in the EnCa101 human endometrial tumor model. We find that increased PKC isozyme expression correlates with hormone-independ ent breast cancer as well as antiestrogen-stimulated endometrial cance r. (C) 1998 Elsevier Science Ltd. All rights reserved.