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Research Article

Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function.

A Zentella, F M Weis, D A Ralph, M Laiho, J Massagué
A Zentella
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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F M Weis
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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D A Ralph
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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M Laiho
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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J Massagué
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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DOI: 10.1128/MCB.11.10.4952
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ABSTRACT

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.

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Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function.
A Zentella, F M Weis, D A Ralph, M Laiho, J Massagué
Molecular and Cellular Biology Oct 1991, 11 (10) 4952-4958; DOI: 10.1128/MCB.11.10.4952

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Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function.
A Zentella, F M Weis, D A Ralph, M Laiho, J Massagué
Molecular and Cellular Biology Oct 1991, 11 (10) 4952-4958; DOI: 10.1128/MCB.11.10.4952
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