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T-Cell Receptor Chain Alternate Reading Frame Protein (TARP) Expression in Prostate Cancer Cells Leads to an Increased Growth Rate and Induction of Caveolins and Amphiregulin

Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892 [C. D. W., B. L., I. P.], and Division of Clinical Immunology, Uppsala University, S-751 85 Uppsala, Sweden [M. E.]

Previously, we showed that prostate and prostate cancer cells express a truncated T-cell receptor chain mRNA that uses an alternative reading frame to produce a novel nuclear T-cell receptor chain alternate reading frame protein (TARP). TARP is expressed in the androgen-sensitive LNCaP prostate cancer cell line but not in the androgen-independent PC3 prostate cancer cell line, indicating that TARP may play a role in prostate cancer progression. To elucidate the function of TARP, we generated a stable PC3 cell line that expresses TARP in a constitutive manner. Expression of TARP in PC3 cells resulted in a more rapid growth rate with a 5-h decrease in doubling time. cDNA microarray analysis of 6538 genes revealed that caveolin 1, caveolin 2, amphiregulin, and melanoma growth stimulatory activity were significantly up-regulated, whereas IL-1ß was significantly down-regulated in PC3 cells expressing TARP. We also demonstrated that TARP expression is up-regulated by testosterone in LNCaP cells that express a functional androgen receptor. These results suggest that TARP has a role in regulating growth and gene expression in prostate cancer cells.

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