Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer

BACKGROUND Androgen and TGF‐β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human...

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Published inThe Prostate Vol. 72; no. 9; pp. 1035 - 1044
Main Authors Mascareno, Eduardo J., Belashov, Ivan, Siddiqui, M. A. Q., Liu, Fang, Dhar-Mascareno, Manya
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.06.2012
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Summary:BACKGROUND Androgen and TGF‐β signaling are important components during the progression of prostate cancer. However, whether common molecular events participate in the activation of these signaling pathways are less understood. METHOD Hexim 1 expression was detected by immunohistochemistry of human tissue microarrays and TRAMP mouse models. The in vivo significance of Hexim‐1 was established by crossing the TRAMP mouse model of prostate cancer with Hexim‐1 heterozygous mice. TRAMP C2 cell line was also modified to delete one copy of Hexim‐1 gene to generate TRAMP‐C2‐Hexim‐1+/− cell lines. RESULTS In this report, we observed that Hexim‐1 protein expression is absent in normal prostate but highly expressed in adenocarcinoma of the prostate and a characteristic sub‐cellular distribution among normal, benign hyperplasia, and adenocarcinoma of the prostate. Heterozygosity of the Hexim‐1 gene in the prostate cancer mice model and the TRAMP‐C2 cell line, leads to increased Cdk9‐dependent serine phosphorylation on protein targets such as the androgen receptor (AR) and the TGF‐β‐dependent downstream transcription factors, such as the SMAD proteins. CONCLUSION Our results suggest that changes in the Hexim‐1 protein expression and cellular distribution significantly influences the AR activation and the TGF‐β signaling. Thus, Hexim‐1 is likely to play a significant role in prostate cancer progression. Prostate 72:1035–1044, 2012. © 2011 Wiley Periodicals, Inc.
Bibliography:istex:2FCBE1860974C1AF2C0B1E786B1B1AA2AF036AD1
ArticleID:PROS21510
ark:/67375/WNG-60B3ZGMV-N
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ISSN:0270-4137
1097-0045
DOI:10.1002/pros.21510