p53-independent role of MDM2 in TGF-beta1 resistance

Sun, P., Dong, P., Dai, K., Hannon, G. J., Beach, D. (December 1998) p53-independent role of MDM2 in TGF-beta1 resistance. Science, 282 (5397). pp. 2270-2. ISSN 0036-8075 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9856953
DOI: 10.1126/science.282.5397.2270

Abstract

Transforming growth factor-beta (TGF-beta) inhibits cell proliferation, and acquisition of TGF-beta resistance has been linked to tumorigenesis. A genetic screen was performed to identify complementary DNAs that abrogated TGF-beta sensitivity in mink lung epithelial cells. Ectopic expression of murine double minute 2 rescued TGF-beta-induced growth arrest in a p53-independent manner by interference with retinoblastoma susceptibility gene product (Rb)/E2F function. In human breast tumor cells, increased MDM2 expression levels correlated with TGF-beta resistance. Thus, MDM2 may confer TGF-beta resistance in a subset of tumors and may promote tumorigenesis by interference with two independent tumor suppressors, p53 and Rb.

Item Type: Paper
Uncontrolled Keywords: Animals Breast Neoplasms/genetics/metabolism/pathology Carrier Proteins Cell Cycle Proteins Cell Division Cell Line Cell Transformation, Neoplastic DNA-Binding Proteins Drug Resistance, Neoplasm E2F Transcription Factors Gene Expression Genes, Retinoblastoma Genes, p53 Genetic Vectors Humans Mice Mink Nuclear Proteins Phosphorylation Proto-Oncogene Proteins/genetics/ physiology Proto-Oncogene Proteins c-mdm2 Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Retinoblastoma Protein/metabolism Signal Transduction Transcription Factor DP1 Transcription Factors/genetics/metabolism Transcription, Genetic Transforming Growth Factor beta/ pharmacology/physiology Tumor Cells, Cultured Tumor Suppressor Protein p53/ physiology
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > MDM2
diseases & disorders > cancer > cancer types > breast cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell division
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > cell line

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > p53
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Hannon lab
CSHL labs > Beach lab
Depositing User: Kathleen Darby
Date: 18 December 1998
Date Deposited: 01 May 2014 12:53
Last Modified: 07 May 2014 13:01
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29935

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