Absence of transforming growth factor-beta responsiveness in the tamoxifen growth-inhibited human breast cancer cell line CAMA-1.
Tamoxifen has been an effective antiestrogen in suppressing breast cancer growth which is estrogen-responsive or dependent. Early studies have provided circumstantial evidence that transforming growth factor-beta (TGF-beta) may be an autocrine mediator of tamoxifen action. Therefore, it is both fundamentally important and clinically relevant to investigate the relationship between tamoxifen and TGF-beta. In this study, we demonstrated that CAMA-1 cells, which are sensitive to tamoxifen inhibition, did not respond to TGF-beta growth inhibition. The type I and II TGF-beta receptors were undetectable by the radio-ligand affinity labeling technique. Despite the presence of a normal TGF-beta type II receptor gene, the mRNA transcript of the gene was undetectable by the extremely sensitive Intron-differential RNA/PCR method. The possibility that the lack of TGF-beta receptors might be intimately linked to the absence of normal retinoblastoma (Rb) gene products, as suggested by previous studies of retinoblastoma cells, was further investigated. The lack of TGF-beta receptor expression was found due to reasons other than the absence, deletion or abnormality of the Rb gene because a normal Rb gene and its hyper- and hypo-phosphorylated protein products were detected in CAMA-1 cells. In conclusion, our results suggest that the TGF-beta system is not obligatory for antiestrogen growth inhibition of CAMA-1 cells.
Ji
H
H
Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis 55455.
Stout
L E
LE
Zhang
Q
Q
Zhang
R
R
Leung
H T
HT
Leung
B S
BS
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004967:Estrogens; D005260:Female; D016161:Genes, Retinoblastoma; D016259:Genes, myc; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000172:deficiency* / Q000235:genetics; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology; D010051:Ovarian Neoplasms / Q000473:pathology; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics; D012175:Retinoblastoma / Q000473:pathology; D016160:Retinoblastoma Protein / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004967:Estrogens; D009363:Neoplasm Proteins; D018125:Receptors, Transforming Growth Factor beta; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D013629:Tamoxifen