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Titolo:
ErbB2-overexpressing human mammary carcinoma cells display an increased requirement for the phosphatidylinositol 3-kinase signaling pathway in anchorage-independent growth
Autore:
Hermanto, U; Zong, CS; Wang, LH;
Indirizzi:
Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA Mt Sinai Sch MedNew York NY USA 10029 Microbiol, New York, NY 10029 USA
Titolo Testata:
ONCOGENE
fascicolo: 51, volume: 20, anno: 2001,
pagine: 7551 - 7562
SICI:
0950-9232(20011108)20:51<7551:EHMCCD>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; PROTEIN-KINASE; INDUCED APOPTOSIS; BREAST-CANCER; UP-REGULATION; S6 KINASE; ONCOGENE; AKT; OVEREXPRESSION; AMPLIFICATION;
Keywords:
ErbB2; PI3 kinase; breast cancer; cell growth;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Wang, LH Mt Sinai Sch Med, Dept Microbiol, 1 Gustave L Levy Pl, New York, NY 10029 USA Mt Sinai Sch Med 1 Gustave L Levy Pl New York NY USA 10029 29 USA
Citazione:
U. Hermanto et al., "ErbB2-overexpressing human mammary carcinoma cells display an increased requirement for the phosphatidylinositol 3-kinase signaling pathway in anchorage-independent growth", ONCOGENE, 20(51), 2001, pp. 7551-7562

Abstract

The proto-oncogene ErbB2 is known to be amplified and to play an importantrole in the development of about one-third of human breast cancers. Phosphatidylinositol 3-kinase (P13K), which is often activated in ErbB2-overexpressing breast cancer cells, is known to regulate cell proliferation and cellsurvival. Selective inhibitors of the P13K pathway were used to assess therelevance of P13K signaling in the anchorage-independent growth of a series of human mammary carcinoma cell lines. Wortmannin, LY294002, and rapamycin at concentrations that did not affect MAPK phosphorylation but substantially inhibited P13K, Akt, and p70(S6K) significantly suppressed the soft agar growth of tumor cell lines that overexpress ErbB2 but not the growth of tumor lines with low ErbB2 expression. A similar growth inhibition of ErbB2-overexpressing carcinoma lines was observed when a dominant negative p85(P13K) mutant was introduced into these cells. Forced expression of ErbB2 in breast cancer lines originally expressing low ErbB2 levels augmented receptor expression and sensitized those lines to LY294002- and rapamycin-mediatedinhibition of colony formation. Furthermore, treatment with LY294002 resulted in the selective increase of cyclin-dependent kinase inhibitors p21(CIP1) or p27(Kipt) and suppression of cyclin E-associated Cdk2 kinase activityin ErbB2-overexpressing lines, which may account for their hypersensitivity toward inhibitors of the P13K pathway in anchorage-independent growth. Our results indicate that the P13K/Akt/p70(S6K) pathway plays an enhanced role in the anchorage-independent growth of ErbB2-overexpressing breast cancercells, therefore providing a molecular basis for the selective targeting of this signaling pathway in the treatment of ErbB2-related human breast malignancies.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/09/20 alle ore 22:28:24