title: Protein kinase D1 (PKD1) influences androgen receptor (AR) function in prostate cancer cells.
abstract: Protein kinase D1 (PKD1), founding member of PKD protein family, is down-regulated in advanced prostate cancer (PCa). We demonstrate that PKD1 and androgen receptor (AR) are present as a protein complex in PCa cells. PKD1 is associated with a transcriptional complex which contains AR and promoter sequence of the Prostate Specific Antigen (PSA) gene. Ectopic expression of wild type PKD1 and the kinase dead mutant PKD1 (K628W) attenuated the ligand-dependent transcriptional activation of AR in prostate cancer cells and yeast cells indicating that PKD1 can affect AR transcription activity, whereas knocking down PKD1 enhanced the ligand-dependent transcriptional activation of AR. Co-expression of kinase dead mutant with AR significantly inhibited androgen-mediated cell proliferation in both LNCaP and DU145 PC cells. Our data demonstrate for the first time that PKD1 can influence AR function in PCa cells.
authors.affiliation: University of Massachusetts Medical School, Division of Urology, Department of Surgery, Worcester, MA 01655, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Mak
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.forename: Viqar
authors.initials: V
authors.lastname: Syed
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
authors.forename: Sazzad
authors.initials: S
authors.lastname: Hassan
authors.forename: Helal
authors.initials: H
authors.lastname: Biswas
authors.forename: K C
authors.initials: KC
authors.lastname: Balaji
mesh_terms: D059002:Androgen Receptor Antagonists; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen; C089212:protein kinase D; D011493:Protein Kinase C; D017430:Prostate-Specific Antigen