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Titolo:
Regulation of Fas ligand expression in breast cancer cells by estrogen: functional differences between estradiol and tamoxifen
Autore:
Mor, G; Kohen, F; Garcia-Velasco, J; Nilsen, J; Brown, W; Song, J; Naftolin, F;
Indirizzi:
Yale Univ, Sch Med, Dept Obstet & Gynecol, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 bstet & Gynecol, New Haven, CT 06520 USA Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel Weizmann Inst Sci Rehovot Israel IL-76100 Biol, IL-76100 Rehovot, Israel
Titolo Testata:
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
fascicolo: 5, volume: 73, anno: 2000,
pagine: 185 - 194
SICI:
0960-0760(200007/08)73:5<185:ROFLEI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
INDUCED APOPTOSIS; RESPONSE ELEMENTS; TUMOR-CELLS; T-CELL; MEDIATED CYTOTOXICITY; TRANSCRIPTION FACTOR; NEGATIVE REGULATOR; IMMUNE PRIVILEGE; RETINOIC ACID; CD95 LIGAND;
Keywords:
FasL; estrogen; tamoxifen; breast cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Mor, G Yale Univ, Sch Med, Dept Obstet & Gynecol, 333 Cedar St,FMB 202, New Haven, CT 06520 USA Yale Univ 333 Cedar St,FMB 202 New Haven CT USA 06520 CT 06520 USA
Citazione:
G. Mor et al., "Regulation of Fas ligand expression in breast cancer cells by estrogen: functional differences between estradiol and tamoxifen", J STEROID B, 73(5), 2000, pp. 185-194

Abstract

During neoplastic growth and metastasis, the immune system responds to thetumor by developing both cellular and humoral immune responses. In spite of this active response, tumor cells escape immune surveillance. We previously showed that FasL expression by breast tumor plays a central role in the induction of apoptosis of infiltrating Fas-immune cells providing the mechanism for tumor immune privilege. In the present study, we showed that FasL in breast tissue is functionally active, and estrogen and tamoxifen regulate its expression. We identified an estrogen recognizing element like-motif in the promoter region of the FasL gene, suggesting direct estrogen effectson FasL expression. This was confirmed by an increase in FasL expression in both RNA and protein levels in hormone sensitive breast cancer cells treated with estradiol. This effect is receptor mediated since tamoxifen blocked the estrogenic effect. Interestingly, tamoxifen also inhibited FasL expression in estrogen-depleted conditions. Moreover, an increase in FasL in breast cancer cells induces apoptosis in Fas bearing T cells and, tamoxifen blocks the induction of apoptosis. These studies provide evidence that tamoxifen inhibits FasL expression, allowing the killing of cancer cells by activated lymphocytes. This partially explains the protective effect of tamoxifen against breast cancer. (C) 2000 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 00:22:46