title: CK2-NCoR signaling cascade promotes prostate tumorigenesis.
abstract: The aberrant expressions of casein kinase 2 (CK2) was found in prostate cancer patient and cell lines, but little is known of the detailed mechanisms implicated in prostate tumorigenesis. In this study, we report that both CK2 activity and CK2-mediated NCoR phosphorylation are significantly elevated in the androgen-independent prostate cancer cell line DU145 and PC-3 compared with RWPE1 and LNCaP cells. Increased phosphorylation inversely correlates with the mRNA level of the NCoR-regulated gene, interferon-γ-inducible protein 10 (IP-10). CK2 inhibition abrogated NCoR phosphorylation, IP-10 transcriptional repression, and the invasion activity of PC-3 cells. Inhibition of the CK2-NCoR network significantly reduced in vivo PC-3 cell tumorigenicity, likely due to transcriptional derepression of IP-10. Clinicopathological analyses revealed that increased CK2-mediated NCoR phosphorylation significantly correlates with poor survival among prostate cancer patients. These findings elucidate a CK2-modulated oncogenic cascade in prostate tumorigenesis.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Beom Jin
authors.initials: BJ
authors.lastname: Lim
authors.forename: Hyo-Kyoung
authors.initials: HK
authors.lastname: Choi
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Jang
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D047390:Casein Kinase II / Q000378:metabolism*; D045744:Cell Line, Tumor; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D056970:Co-Repressor Proteins; D047390:Casein Kinase II