RÉSUMÉ
Our present study demonstrates that the isoflavone genistein exerts a differential response in normal and malignant breast epithelial cells. The addition of genistein results in a dose-dependent increase in TGF-beta 1 mRNA expression in normal human mammary epithelial cells (HMEC) but not in tumor-derived MCF-7 cells. Genistein inhibits the growth and also causes an increase in apoptosis of HMEC. The increased expression of TGF-beta 1 may contribute to the growth inhibitory as well as apoptotic effects of genistein on HMEC.
Sujet(s)
Tumeurs du sein/métabolisme , Région mammaire/métabolisme , Cellules épithéliales/métabolisme , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , Génistéine/pharmacologie , Facteur de croissance transformant bêta/biosynthèse , Apoptose/effets des médicaments et des substances chimiques , Région mammaire/cytologie , Tumeurs du sein/anatomopathologie , Division cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Cellules épithéliales/cytologie , Cellules épithéliales/anatomopathologie , Femelle , Humains , Cinétique , ARN messager/biosynthèse , Transcription génétique/effets des médicaments et des substances chimiques , Cellules cancéreuses en cultureRÉSUMÉ
Organic cation (OC+)/H+ exchangers are found in several mammalian tissues and in numerous organisms. In the kidney OC+/H+ exchange activity is localized to the brush border membrane of the proximal tubule cells of the nephron and is believed to be responsible for the efflux of numerous xenobiotics from the tubule cell into the tubular fluid. The objective of the present study was to identify the OC+/H+ exchanger in brush border membrane vesicles isolated from dog kidney by photoaffinity labeling. The results show that [3H]azidopine is an ideal photoaffinity labeling reagent; in the dark it binds reversibly, but irreversibly after photoactivation. The photoaffinity labeling reaction is efficient, specific and sensitive. Our findings are consistent with the conclusions that a 41-kDa protein is the exchanger and that it is present at a concentration of 780 +/- 140 fmol/mg membrane protein (n = 4). A 49-kDa protein is labeled to some extent as well. The relationship between the 41- and 49-kDa proteins has not been resolved.