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PMID: 1922028 Published · ppublish English Journal Article

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

Molecular and cellular biology ·Vol. 11 ·No. 10 ·1991-10-00 ·Pages 4952-8

Zentella A, Weis FM, Ralph DA, Laiho M, Massagué J

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.

Related Genes
RB
MeSH Terms
Animals Blotting, Northern Cell Cycle/drug effects Cell Line Down-Regulation/drug effects Genes, Retinoblastoma Humans Kinetics Mink Mutation/genetics Oncogene Protein p65(gag-jun)/genetics Plasminogen Inactivators Proto-Oncogene Proteins c-myc/genetics Retinoblastoma Protein/physiology Transcription, Genetic/drug effects Transforming Growth Factor beta/pharmacology Tumor Cells, Cultured
Chemicals
Oncogene Protein p65(gag-jun) Plasminogen Inactivators Proto-Oncogene Proteins c-myc Retinoblastoma Protein Transforming Growth Factor beta
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zentella A
Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Weis F M
Ralph D A
Laiho M
Massagué J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.11.10.4952-4958.1991
Published
1991-10-00
Pages
4952-8
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361474
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.11.10.4952-4958.1991 PMC Full Text View journal details
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