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Titolo:
Regulation of cell cycle and cyclins by 16 alpha-hydroxyestrone in MCF-7 breast cancer cells
Autore:
Lewis, JS; Thomas, TJ; Klinge, CM; Gallo, MA; Thomas, T;
Indirizzi:
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey New Brunswick NJ USA 08903swick, NJ 08903 USA Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Community & Environm Med, New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey New Brunswick NJ USA 08903 swick, NJ 08903 USA Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey New Brunswick NJ USA 08903 swick, NJ 08903 USA Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA Univ Louisville Louisville KY USA 40292 ol Biol, Louisville, KY 40292 USA Rutgers State Univ, Nutr Sci Grad Program, New Brunswick, NJ 08903 USA Rutgers State Univ New Brunswick NJ USA 08903 New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey New Brunswick NJ USA 08903 swick, NJ 08903 USA
Titolo Testata:
JOURNAL OF MOLECULAR ENDOCRINOLOGY
fascicolo: 3, volume: 27, anno: 2001,
pagine: 293 - 307
SICI:
0952-5041(200112)27:3<293:ROCCAC>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESTROGEN RESPONSE ELEMENTS; DEPENDENT KINASES; ESTRADIOL METABOLITES; RECEPTOR-BINDING; GENE-EXPRESSION; CDK INHIBITORS; TISSUE-CULTURE; KAPPA-B; ACTIVATION; PHOSPHORYLATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Thomas, T Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Clin Acad Bldg,Room 7090,125 Paterson St, New Brunswick, NJ 08903 USA Univ Med & Dent New Jersey Clin Acad Bldg,Room 7090,125 Paterson St New Brunswick NJ USA 08903
Citazione:
J.S. Lewis et al., "Regulation of cell cycle and cyclins by 16 alpha-hydroxyestrone in MCF-7 breast cancer cells", J MOL ENDOC, 27(3), 2001, pp. 293-307

Abstract

It has been suggested that alterations in estradiol (E-2) metabolism, resulting in increased production of 16 alpha -hydroxyestrone (16 alpha -OHE1),is associated with an increased risk of breast cancer. In the present study, we examined the effects of 16 alpha -OHE1, on DNA synthesis, cell cycle progression, and the expression of cell cycle regulatory genes in MCF-7 breast cancer cells. G(1) synchronized cells were treated with 1 to 25 nM 16 alpha -OHE1, for 24 and 48 h. [H-3]Thymidine incorporation assay showed that16 alpha -OHE1, caused an 8-fold increase in DNA synthesis compared with that of control cells, whereas E-2 caused a 4-fold increase. Flow cytometricanalysis of cell cycle progression also demonstrated the potency of 16 alpha -OHE1 in stimulating cell growth. When G(1) synchronized cells were treated with 10 nM 16 alpha -OHE1 for 24 h, 62 +/- 3% of cells were in S phase compared with 14 +/- 3% and 52 +/- 2% of cells in the control and E-2-treated groups respectively. In order to explore the role of 16 alpha -OHE1, in cell cycle regulation, we examined its effects on cyclins (D1, E, A, B1), cyclin dependent kinases (Cdk4, Cdk2), and retinoblastoma protein (pRB) using Western and Northern blot analysis. Treatment of cells with 10 nM 16 alpha -OHE1, resulted in 4- and 3-fold increases in cyclin D1 and cyclin A, respectively, at the protein level. There was also a significant increase in pRB phosphorylation and Cdk2 activation. In addition, transient transfectionassay using an estrogen response element-driven luciferase reporter vectorshowed a 15-fold increase in estrogen receptor-mediated transactivation compared with control. These results show that 16 alpha -OHE, is a potent estrogen capable of accelerating cell cycle kinetics and stimulating the expression of cell cycle regulatory proteins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 06:20:05