Defects of TGF-beta receptor signaling in mammary cell tumorigenesis.
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.
Brattain
M G
MG
Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo 43699-0008, USA.
Ko
Y
Y
Banerji
S S
SS
Wu
G
G
Willson
J K
JK
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*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta