Zentella A, Weis F M, Ralph D A, Laiho M, Massagué J
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Mol Cell Biol. 1991 Oct;11(10):4952-8. doi: 10.1128/mcb.11.10.4952-4958.1991.
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.
视网膜母细胞瘤易感基因产物RB的生长抑制功能，与转化生长因子β1（TGF-β1）介导的生长抑制及某些增殖相关基因的负调控有关。为了确定早期基因对TGF-β1的反应对细胞周期和RB生长抑制功能的依赖性，对其进行了研究。TGF-β1能迅速提高junB和PAI-1 mRNA的稳态水平，并降低c-myc mRNA的稳态水平，在含有磷酸化状态RB的Mv1Lu肺上皮细胞的S期群体中诱导这些反应。由于在此状态下RB被认为缺乏生长抑制活性，因此也在其突变RB产物缺乏生长抑制功能的DU145人前列腺癌细胞中检测了对TGF-β1的反应。在这些细胞中，TGF-β1也在转录起始水平降低c-myc的表达。这些结果表明，c-myc、junB和PAI-1对TGF-β1的反应并不局限于细胞周期的G1期，且TGF-β1对c-myc表达的下调可通过一种独立于RB生长抑制功能的机制发生。
