title: Defects of TGF-beta receptor signaling in mammary cell tumorigenesis.
abstract: Transforming growth factor beta (TGF-beta) receptor expression and signal transduction in human breast cancer are reviewed as a function of estrogen receptor (ER) expression. ER+ breast cancer cells are generally resistant to the inhibitory effects of TGF-beta. The only known exception appears to be MCF-7 early passage cells which are initially sensitive to TGF-beta, but gain resistance after long-term passage in tissue culture. A number of studies have shown that loss of sensitivity is due to inadequate TGF-beta type II (TGFRII) receptor expression. Stable transfection of TGFRII into ER+ breast cancer cell lines results in the acquisition of TGF-beta sensitivity and reversion of malignancy. Although there are exceptions, ER- breast cancer cells usually express TGFRII, but nevertheless show a low level of sensitivity to TGF-beta. Thus resistance in these cells implies a postreceptor mechanism. Given the frequency with which loss of TGF-beta sensitivity has been associated with loss of TGFRII, the ER- breast cancer cell lines may represent valuable models for identifying postreceptor mechanisms of resistance.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo 43699-0008, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Brattain
authors.forename: Y
authors.initials: Y
authors.lastname: Ko
authors.forename: S S
authors.initials: SS
authors.lastname: Banerji
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: J K
authors.initials: JK
authors.lastname: Willson
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta