title: Hexim-1 modulates androgen receptor and the TGF-β signaling during the progression of prostate cancer.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cell Biology, State University of New York, Downstate Medical School, Brooklyn, New York 11203, USA. emascareno@downstate.edu
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Mascareno
authors.forename: Ivan
authors.initials: I
authors.lastname: Belashov
authors.forename: M A Q
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Manya
authors.initials: M
authors.lastname: Dhar-Mascareno
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D051785:Smad Proteins / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology
chemical_list: C118642:Hexim1 protein, mouse; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; D051785:Smad Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta