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Estrogen synthesis in human colon cancer epithelial cells.
Fiorelli, G; Picariello, L; Martineti, V; Tonelli, F; Brandi, M L.
Afiliação
  • Fiorelli G; Endocrine Unit, Department of Clinical Physiopathology, Medical School, University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
J Steroid Biochem Mol Biol ; 71(5-6): 223-30, 1999 Dec 31.
Article em En | MEDLINE | ID: mdl-10704911
ABSTRACT
Epidemiological and experimental data suggest an involvement of estrogen in the development and progression of colorectal cancer. In order to determine whether local synthesis of estrogen occurred in human colonic cancer cells, two colorectal cancer cell lines, HCT8 and HCT116, were evaluated for gene expression and enzyme activity of cytochrome P450 aromatase. In addition, the effect on aromatase expression of charcoal-stripped fetal calf serum, of quercetin and genistein and of tamoxifen and raloxifene was investigated in both cell lines. RT-PCR analysis revealed that colorectal adenocarcinoma cell lines contain aromatase as a major component. The conversion of [(3)H]-androstenedione to estrone and labeled water was dose-dependently inhibited by 4-hydroxyandrostenedione and obeyed Michaelis-Menten kinetic with apparent Km values of approximately 20 nM and V(max) values of approx. 200 and 500 fmol/mg protein/h for HCT8 and HCT116 cells, respectively. After 24 h incubation, genistein (1 microM) significantly increased aromatase activity in HCT8 cells, with no effect on HCT116 cells. In accord with previous observation in reproductive tissues, quercetin (1 microM) significantly inhibited the enzyme activity in both cell lines. Also tamoxifen (100 nM) acted as inhibitor, while raloxifene (10 nM) decreased the enzyme activity only in HCT116 cells. The aromatase gene expression modulation by these effective agents was consistent with their effects on enzyme activity. These findings demonstrate for the first time that colorectal adenocarcinoma cell lines express aromatase. Interestingly, the enzyme activity was inhibited by quercetin, one major dietary flavonoid, by tamoxifen, a hormonal therapeutic agent for breast cancer, and by raloxifene, used in the prevention of postmenopausal osteoporosis.
Assuntos
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Base de dados: MEDLINE Assunto principal: Aromatase / Neoplasias Colorretais / Estrogênios Idioma: En Ano de publicação: 1999 Tipo de documento: Article
Buscar no Google
Base de dados: MEDLINE Assunto principal: Aromatase / Neoplasias Colorretais / Estrogênios Idioma: En Ano de publicação: 1999 Tipo de documento: Article