Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function.
The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth-suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth-suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB.
Zentella
A
A
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Weis
F M
FM
Ralph
D A
DA
Laiho
M
M
Massagué
J
J
D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle / Q000187:drug effects*; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D016161:Genes, Retinoblastoma; D006801:Humans; D007700:Kinetics; D008907:Mink; D009154:Mutation / Q000235:genetics; D016759:Oncogene Protein p65(gag-jun) / Q000235:genetics; D015849:Plasminogen Inactivators; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016160:Retinoblastoma Protein / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016759:Oncogene Protein p65(gag-jun); D015849:Plasminogen Inactivators; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta