Early gene responses to transforming growth-factor-β in cells lacking growth-suppressive RB function Journal Article


Authors: Zentella, A.; Weis, F. M. B.; Ralph, D. A.; Laiho, M.; Massagué, J.
Article Title: Early gene responses to transforming growth-factor-β in cells lacking growth-suppressive RB function
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.
Keywords: signal transduction; c-myc; patterns; tgf-beta; messenger-rna; retinoblastoma susceptibility gene; sv40 large-t; exhibit distinct; receptor type-i; different members; concomitant loss
Journal Title: Molecular and Cellular Biology
Volume: 11
Issue: 10
ISSN: 0270-7306
Publisher: American Society for Microbiology  
Date Published: 1991-10-01
Start Page: 4952
End Page: 4958
Language: English
ACCESSION: WOS:A1991GJ40100017
DOI: 10.1128/mcb.11.10.4952
PROVIDER: wos
PMCID: PMC361474
PUBMED: 1922028
Notes: Source: Wos
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  1. Joan Massague
    389 Massague
  2. Marikki Laiho
    12 Laiho