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

Eduardo J. Mascareno, Ivan Belashov, M. A.Q. Siddiqui, Fang Liu, Manya Dhar-Mascareno

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1035-1044
Number of pages10
JournalProstate
Volume72
Issue number9
DOIs
StatePublished - Jun 15 2012

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Keywords

  • HEXIM1
  • RNA polymerase
  • SMAD phosphorylation
  • TGF-β
  • androgen receptor
  • mouse model
  • prostate cancer
  • serine phosphorylation

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