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Titolo:
Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells
Autore:
Burke, WM; Jin, XH; Lin, HJ; Huang, M; Liu, R; Reynolds, RK; Lin, JY;
Indirizzi:
Univ Michigan, Ctr Comprehens Canc, Div Gynecol Oncol, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 t & Gynecol, Ann Arbor, MI 48109 USA
Titolo Testata:
ONCOGENE
fascicolo: 55, volume: 20, anno: 2001,
pagine: 7925 - 7934
SICI:
0950-9232(20011129)20:55<7925:IOCASS>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHEMOTHERAPY-INDUCED APOPTOSIS; BCL-X-L; CARCINOMA CELLS; KINASE-ACTIVITY; ACTIVATION; BCL-X(L); FAMILY; PHOSPHORYLATION; TRANSCRIPTION; RESISTANCE;
Keywords:
Stat3; AG490; Bcl-X-L; JAK2; apoptosis; ovarian cancer; breast cancer;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Lin, JY Univ Michigan, Ctr Comprehens Canc, Div Gynecol Oncol, Dept Obstet& Gynecol, 1500 E Med Ctr Dr,CCGC 4215, Ann Arbor, MI 48109 USA Univ Michigan 1500 E Med Ctr Dr,CCGC 4215 Ann Arbor MI USA 48109 A
Citazione:
W.M. Burke et al., "Inhibition of constitutively active Stat3 suppresses growth of human ovarian and breast cancer cells", ONCOGENE, 20(55), 2001, pp. 7925-7934

Abstract

Signal transducers and activators of transcription (STATs) are transcription factors activated in response to cytokines and growth factors. Constitutively active Stat3 has been shown to mediate oncogenic transformation in cultured cells and induce tumor formation in mice. An increasing number of tumor-derived cell lines as well as samples from human cancer have been reported to express constitutively active Stat3 protein. We previously demonstrated that ovarian cancer cell lines express high levels of constitutively active Stat3. In this study, we show that inhibition of the Stat3 signaling pathway using the Janus Kinase-selective inhibitor, AG490, and a dominant negative Stat3 (Stat3 beta) significantly suppresses the growth of ovarian and breast cancer cell lines harboring constitutively active Stat3. In the ovarian cancer cell lines, AG490 also diminished the phosphorylation of Stat3, Stat3 DNA binding activity, and the expression of Bcl-X-L. Further, AG490induced significant apoptosis in ovarian and breast cancer cell lines expressing high levels of constitutively active Stat3 but had a less profound effect on normal cells lacking constitutively active Stat3. AG490 also enhanced apoptosis induced by cisplatin in ovarian cancer cells. These results suggest that inhibition of Stat3 signaling may provide a potential therapeutic approach for treating ovarian and breast cancers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 07:39:55