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Molecular and Cellular Biology, January 1999, p. 899-908, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Coactivator PC4 Mediates AP-2 Transcriptional Activity and Suppresses ras-Induced Transformation Dependent on AP-2 Transcriptional Interference

Perry Kannan1 and Michael A. Tainsky2,*

MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio 44109,1 and Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 770302

Received 19 May 1998/Returned for modification 6 August 1998/Accepted 17 September 1998

ras oncogene-transformed PA-1 human teratocarcinoma cells have abundant AP-2 mRNA but, paradoxically, little AP-2 transcriptional activity. We have previously shown that overexpression of AP-2 in nontumorigenic variants of PA-1 cells results in inhibition of AP-2 activity and induction of tumorigenicity similar to that caused by ras transformation of PA-1 cells. Evidence indicated the existence of a novel mechanism of inhibition of AP-2 activity involving sequestering of transcriptional coactivators. In this study, we found that PC4 is a positive coactivator of AP-2 and can restore AP-2 activity in ras-transformed PA-1 cells. Relative to vector-transfected ras cell lines, ras cell lines stably transfected with and expressing the PC4 cDNA have a diminished growth rate and exhibit a loss of anchorage-independent growth, and they are unable to induce the formation of tumors in nude mice. These data suggest that a transcriptional coactivator, like a tumor suppressor, can have a growth-suppressive effect on cells. Our experiments are the first to show that ras oncogenes and oncogenic transcription factors can induce transformation through effects on the transcription machinery rather than through specific programs of gene expression.

* Corresponding author. Present address: Program in Cancer Genetics, The Barbara Ann Karmanos Cancer Institute, Wayne State University, 110 E. Warren Ave., Detroit, MI 48201. Phone: (313) 833-0715, ext. 2641. Fax: (313) 832-7294. E-mail: tainskym{at}karmanos.org.

Molecular and Cellular Biology, January 1999, p. 899-908, Vol. 19, No. 1
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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