title: Androgen receptor and heterogeneous nuclear ribonucleoprotein K colocalize in the nucleoplasm and are modulated by bicalutamide and 4-hydroxy-tamoxifen in prostatic cancer cell lines.
abstract: BACKGROUND
  Bicalutamide (BIC) is widely used in prostate cancer therapy. The dose and schedule employed are well tolerated, but about 50% of patients develop gynecomastia. Several studies have shown a significant reduction of the troublesome effects when Tamoxifen is concomitantly administered with BIC. However, the results reported in the literature seem to be preliminary and possible interferences could be present. In order to clarify the molecular mechanisms of the combination of the two drugs, we have investigated whether the expression of the proteins belonging to nuclear matrix (NM), one modulator of hormone action, is altered by BIC and/or 4-hydroxy-tamoxifen (4OHT) in LNCaP cells. We focused above all on heterogeneous nuclear ribonucleoprotein K (hnRNP K) a NM protein with a key role in prostate carcinoma.
  
  
  METHODS
  NM proteins were analyzed by two-dimensional gel electrophoresis. Modulation and compartmentalization of the androgen receptor and the hnRNP K were studied by Western blotting, confocal microscopy, and immunoprecipitation.
  
  
  RESULTS
  Proteomic analysis revealed that there is a similarity in the changes of the NM proteins elicited by drugs alone but that their combination does not result in a simple additive effect. Moreover, we found that in the nucleoplasm the androgen receptor and the hnRNP K colocalize in a complex that is highly proximal to DNA and that both proteins were synchronously modulated by BIC and/or 4OHT treatment.
  
  
  CONCLUSIONS
  This study confirm the pivotal role of hnRNP K in prostate carcinoma and suggest that this role might be played by the interaction with the androgen receptor.
authors.affiliation: Istituto Nazionale per la Ricerca sul Cancro, Università di Genova, Largo Rosanna Benzi, Genova, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Barboro
authors.forename: Erica
authors.initials: E
authors.lastname: Repaci
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ferrari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Rubagotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
authors.forename: Cecilia
authors.initials: C
authors.lastname: Balbi
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry*; D002470:Cell Survival; D004965:Estrogen Antagonists / Q000494:pharmacology*; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000032:analysis* / Q000502:physiology; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D010766:Phosphorylation; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014105:Tosyl Compounds / Q000494:pharmacology*
chemical_list: D000726:Androgen Antagonists; D000813:Anilides; D004965:Estrogen Antagonists; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D013629:Tamoxifen; C016601:afimoxifene; C053541:bicalutamide; D017430:Prostate-Specific Antigen