TY - JOUR
T1 - Antiestrogen stimulated human endometrial cancer growth
T2 - Laboratory and clinical considerations
AU - Tonetti, Debra A.
AU - O'Regan, Ruth
AU - Tanjore, Shashikala
AU - England, Gale
AU - Jordan, V. Craig
N1 - Funding Information:
We are grateful for the continuing support of the Lynn Sage Foundation of Northwestern Memorial Hospital and to Dr P. G. Satyaswaroop for the gift of EnCa101 in 1987. The studies described here were supported in part by Breast Cancer Program Grant 1P20 CA65764-01 (V. C. J.) and American Cancer Society Grant # 97-27 (D. A. T.).
PY - 1998/4
Y1 - 1998/4
N2 - The new antiestrogen toremifene (TOR) is currently on the market for the 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 effect of TAM on the uterus and the 2-3- fold increased incidence in endometrial carcinoma detected in patients receiving TAM therapy, it is imperative to investigate the effect of TOR on endometrial carcinoma. We compared the actions of TAM and TOR on the EnCa101 human endometrial tumor model and find that both antiestrogens have similar growth stimulatory effects. To investigate a potential mechanism of antiestrogen-stimulated endometrial tumor growth, we have examined known activators of the AP-1 signal transduction pathway, the protein kinase C (PKC) family of isozymes, in the EnCa101 human endometrial tumor model. We find that increased PKC isozyme expression correlates with hormone- independent breast cancer as well as antiestrogen-stimulated endometrial cancer.
AB - The new antiestrogen toremifene (TOR) is currently on the market for the 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 effect of TAM on the uterus and the 2-3- fold increased incidence in endometrial carcinoma detected in patients receiving TAM therapy, it is imperative to investigate the effect of TOR on endometrial carcinoma. We compared the actions of TAM and TOR on the EnCa101 human endometrial tumor model and find that both antiestrogens have similar growth stimulatory effects. To investigate a potential mechanism of antiestrogen-stimulated endometrial tumor growth, we have examined known activators of the AP-1 signal transduction pathway, the protein kinase C (PKC) family of isozymes, in the EnCa101 human endometrial tumor model. We find that increased PKC isozyme expression correlates with hormone- independent breast cancer as well as antiestrogen-stimulated endometrial cancer.
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U2 - 10.1016/S0960-0760(98)00011-9
DO - 10.1016/S0960-0760(98)00011-9
M3 - Article
C2 - 9699872
AN - SCOPUS:0032052776
SN - 0960-0760
VL - 65
SP - 181
EP - 189
JO - Journal of Steroid Biochemistry and Molecular Biology
JF - Journal of Steroid Biochemistry and Molecular Biology
IS - 1-6
ER -