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Titolo:
GROWTH SUPPRESSION OF MCF-7 HUMAN BREAST-CANCER CELLS BY AROMATASE INHIBITORS - A NEW SYSTEM FOR AROMATASE INHIBITOR SCREENING
Autore:
KITAWAKI J; KIM T; KANNO H; NOGUCHI T; YAMAMOTO T; OKADA H;
Indirizzi:
KYOTO PREFECTURAL UNIV MED,DEPT OBSTET & GYNECOL,KAWARAMACHI HIROKOJI,KAMIKYO KU KYOTO 602 JAPAN
Titolo Testata:
Journal of steroid biochemistry and molecular biology
fascicolo: 4-6, volume: 44, anno: 1993,
pagine: 667 - 670
SICI:
0960-0760(1993)44:4-6<667:GSOMHB>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
ESTROGEN BIOSYNTHESIS; AMINOGLUTETHIMIDE; CARCINOMA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
12
Recensione:
Indirizzi per estratti:
Citazione:
J. Kitawaki et al., "GROWTH SUPPRESSION OF MCF-7 HUMAN BREAST-CANCER CELLS BY AROMATASE INHIBITORS - A NEW SYSTEM FOR AROMATASE INHIBITOR SCREENING", Journal of steroid biochemistry and molecular biology, 44(4-6), 1993, pp. 667-670

Abstract

In our previous study we found that MCF-7 cells possess aromatase activity and stimulate estrogen receptor-mediated growth. The pathways through which androgens are converted to estrogens by aromatase and estrogens interact with estrogen receptors contribute significantly to growth stimulation. The administration of aromatase inhibitor results in suppression of growth stimulation by androgens. This system enabled usto assess directly the biological activities of aromatase inhibitors. Aromatase activity was inhibited in a dose-dependent manner by the addition of aminoglutethimide and CGS 16949A, competitive inhibitors, and of 14alpha-hydroxy-4-androstene-3,6,17-trione and 4-hydroxy-androstenedione, mechanism-based inhibitors. After preincubation with mechanism-based inhibitors, aromatase activity was significantly suppressed, whereas after preincubation with competitive inhibitors, it was adversely increased. These effects were concentration- and time-dependent. Preincubation with competitive inhibitors resulted in augmentation of subsequent androgen stimulation of thymidine incorporation, while preincubation with mechanism-based inhibitors resulted in diminished stimulation by subsequent androgen administration. These results suggest thatin MCF-7 cells competitive inhibitors adversely induce aromatase and accelerate the subsequent androgen stimulation of DNA synthesis. Suicide inhibitors are more effective than competitive inhibitors. This system will be useful for aromatase inhibitor screening.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 00:50:34