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Molecular and Cellular Biology, November 2003, p. 7742-7755, Vol. 23, No. 21
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.21.7742-7755.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of the Steroid Receptor Coactivator SRC-3 in Cell Growth

Ge Zhou,1 Yoshihiro Hashimoto,1 Inseok Kwak,1 Sophia Y. Tsai,1,2 and Ming-Jer Tsai1,2*

Department of Molecular and Cellular Biology,1 Department of Medicine, Baylor College of Medicine, Houston, Texas 770302

Received 3 April 2003/ Returned for modification 29 May 2003/ Accepted 30 July 2003

Steroid receptor coactivator 3 (SRC-3/p/CIP/AIB1/ACTR/RAC3/TRAM-1) is a member of the p160 family of nuclear receptor coactivators, which includes SRC-1 (NCoA-1) and SRC-2 (TIF2/GRIP1/NCoA2). Previous studies indicate that SRC-3 is required for normal animal growth and is often amplified or overexpressed in many cancers, including breast and prostate cancers. However, the mechanisms of SRC-3-mediated growth regulation remain unclear. In this study, we show that overexpression of SRC-3 stimulates cell growth to increase cell size in prostate cancer cell lines. Furthermore, our results indicate that overexpression of SRC-3 can modulate the AKT signaling pathway in a steroid-independent manner, which results in the activation of AKT/mTOR signaling concomitant with an increase in cell size. In contrast, down-regulation of SRC-3 expression in cells by small interfering RNA decreases cell growth, leading to a smaller cell size. Similarly, in SRC-3 null mutant mice, AKT signaling is down-regulated in normally SRC-3-expressing tissues. Taken together, these results suggest that SRC-3 is an important modulator for mammalian cell growth.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6253. Fax: (713) 798-8227. E-mail: mtsai{at}bcm.tmc.edu.

Molecular and Cellular Biology, November 2003, p. 7742-7755, Vol. 23, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.21.7742-7755.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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