title: Regucalcin is an androgen-target gene in the rat prostate modulating cell-cycle and apoptotic pathways.
abstract: BACKGROUND
  Regucalcin (RGN) is a calcium (Ca(2+) )-binding protein underexpressed in prostate adenocarcinoma comparatively to non-neoplastic prostate or benign prostate hyperplasia cases. Moreover, RGN expression is negatively associated with the cellular differentiation of prostate adenocarcinoma, suggesting that loss of RGN may be associated with tumor onset and progression. However, the RGN actions over the control of prostate cell growth have not been investigated.
  
  
  METHODS
  Androgens are implicated in the promotion of prostate cell proliferation, thus we studied the in vivo effect of androgens on RGN expression in rat prostate. The role of RGN modulating cell proliferation and apoptotic pathways in rat prostate was investigated using transgenic animals (Tg-RGN) overexpressing the protein.
  
  
  RESULTS
  In vivo stimulation with 5α-dihydrotestosterone (DHT) down-regulated RGN expression in rat prostate. Cell proliferation index and prostate weight were reduced in Tg-RGN, which was concomitant with altered expression of cell-cycle regulators. Tg-RGN presented diminished expression of the oncogene H-ras and increased expression of cell-cycle inhibitor p21. Levels of anti-apoptotic Bcl-2, as well as the Bcl-2/Bax protein ratio were increased in prostates overexpressing RGN. Both caspase-3 expression and enzyme activity were decreased in the prostates of Tg-RGN.
  
  
  CONCLUSIONS
  Overexpression of RGN resulted in inhibition of cell proliferation and apoptotic pathways, which demonstrated its role maintaining prostate growth balance. Thus, deregulation of RGN expression may be an important event favoring the development of prostate cancer. Moreover, the DHT effect down-regulating RGN expression in rat prostate highlighted for the importance of this protein in prostatic physiology.
authors: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors: Cátia V
authors: CV
authors: Vaz
authors: Cláudio J
authors: CJ
authors: Maia
authors: Ricardo
authors: R
authors: Marques
authors: Inês M
authors: IM
authors: Gomes
authors: Sara
authors: S
authors: Correia
authors: Marco G
authors: MG
authors: Alves
authors: José E
authors: JE
authors: Cavaco
authors: Pedro F
authors: PF
authors: Oliveira
authors: Sílvia
authors: S
authors: Socorro
mesh_terms: D000728:Androgens / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D002265:Carboxylic Ester Hydrolases; D002453:Cell Cycle / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D006131:Growth Inhibitors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008297:Male; D011467:Prostate / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017208:Rats, Wistar; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000728:Androgens; D002135:Calcium-Binding Proteins; D006131:Growth Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D002265:Carboxylic Ester Hydrolases; C513325:Rgn protein, rat
keywords: androgen; apoptosis; proliferation; prostate; regucalcin