Faculty Collaboration Database

Overexpression of the tumor suppressor gene Smad4/DPC4 induces p21waf1 expression and growth inhibition in human carcinoma cells. Cancer Res 1998 Dec 15;58(24):5656-61

Date

12/29/1998

Pubmed ID

9865717

Scopus ID

2-s2.0-0032535017 (requires institutional sign-in at Scopus site)   49 Citations

Abstract

The Smad4/DPC4 protein functions as a key transcription factor in transforming growth factor beta (TGF-beta) signaling pathways. However, the downstream target genes regulated by Smad4/DPC4 have not been identified until now. We previously demonstrated that the loss of TGF-beta-induced p21waf1 expression and growth inhibition correlates with inactivation of the Smad4/DPC4 gene. Now we show that transient overexpression of Smad4/DPC4 can induce p21waf1 expression, specific Smad4 DNA binding activity, SBE4-luc reporter gene activity, and subsequent growth inhibition in Smad4/DPC4-null cells and other carcinoma cells in the presence or absence of TGF-beta. Taken together, these data show that p21waf1 is one of the Smad4/DPC4-regulated downstream target genes and suggest that overexpression of the Smad4/DPC4 gene can bypass TGF-beta receptor activation and reestablish one of the key regulatory controls of cell proliferation.

Author List

Hunt KK, Fleming JB, Abramian A, Zhang L, Evans DB, Chiao PJ

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Carcinoma
Cell Division
Cyclin-Dependent Kinase Inhibitor p21
Cyclins
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Signal Transduction
Smad4 Protein
Trans-Activators
Transforming Growth Factor beta
Tumor Cells, Cultured