Publication Date:
1998-12-18
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, P -- Dong, P -- Dai, K -- Hannon, G J -- Beach, D -- New York, N.Y. -- Science. 1998 Dec 18;282(5397):2270-2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9856953" target="_blank"〉PubMed〈/a〉
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
;
Retinoblastoma Protein/metabolism
;
Retinoblastoma-Binding Protein 1
;
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
