Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways

S. Chung, M. Furihata, K. Tamura, M. Uemura, Y. Daigo, Yasutomo Nasu, T. Miki, T. Shuin, T. Fujioka, Y. Nakamura, H. Nakagawa

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Prostate cancer (PC) is the most common malignancy in males. Despite high response rates and clinical benefits, androgen-ablation therapy is ineffective for advanced or relapsed PC because of the emergence of aggressive castration-resistant prostate cancer (CRPC). Through our genome-wide gene expression analysis of PC cells purified from clinical CRPC tissues, we here identified a novel molecular target, PKIB (cAMP-dependent protein kinase inhibitor-β), which was overexpressed specifically in CRPCs and aggressive PCs. Immunohistochemical analysis confirmed its overexpression in CRPCs and its strong correlation with high Gleason scores of PCs. Knockdown of PKIB by siRNA resulted in drastic growth suppression of PC cells, and, concordantly, exogenous introduction of PKIB into PC cells enhanced their growth and mobility. We found the direct interaction between PKIB and cAMP-dependent protein kinase A catalytic subunit (PKA-C), and showed that knockdown of PKIB in PC cells diminished the nuclear translocation of PKA-C. Knockdown of PKIB also decreased the phosphorylation level of Akt at Ser473 in PC cells, and exogenous PKIB introduction enhanced Akt phosphorylation in PC cells by incorporating with endogenous PKA-C kinase. In vitro kinase assay validated the recombinant PKIB enhanced phosphorylation of Akt at Ser473 by PKA-C kinase. These findings show that PKIB and PKA-C kinase can have critical functions of aggressive phenotype of PCs through Akt phosphorylation and that they should be a promising molecular target for PC treatment.

Original languageEnglish
Pages (from-to)2849-2859
Number of pages11
JournalOncogene
Volume28
Issue number32
DOIs
Publication statusPublished - Aug 13 2009

Fingerprint

Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Prostatic Neoplasms
Catalytic Domain
Phosphotransferases
Phosphorylation
Castration
Neoplasm Grading
Growth
Small Interfering RNA
Androgens

Keywords

  • Akt phosphorylation
  • CRPC
  • PKIB
  • Protein kinase A

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Chung, S., Furihata, M., Tamura, K., Uemura, M., Daigo, Y., Nasu, Y., ... Nakagawa, H. (2009). Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways. Oncogene, 28(32), 2849-2859. https://doi.org/10.1038/onc.2009.144

Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways. / Chung, S.; Furihata, M.; Tamura, K.; Uemura, M.; Daigo, Y.; Nasu, Yasutomo; Miki, T.; Shuin, T.; Fujioka, T.; Nakamura, Y.; Nakagawa, H.

In: Oncogene, Vol. 28, No. 32, 13.08.2009, p. 2849-2859.

Research output: Contribution to journalArticle

Chung, S, Furihata, M, Tamura, K, Uemura, M, Daigo, Y, Nasu, Y, Miki, T, Shuin, T, Fujioka, T, Nakamura, Y & Nakagawa, H 2009, 'Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways', Oncogene, vol. 28, no. 32, pp. 2849-2859. https://doi.org/10.1038/onc.2009.144
Chung, S. ; Furihata, M. ; Tamura, K. ; Uemura, M. ; Daigo, Y. ; Nasu, Yasutomo ; Miki, T. ; Shuin, T. ; Fujioka, T. ; Nakamura, Y. ; Nakagawa, H. / Overexpressing PKIB in prostate cancer promotes its aggressiveness by linking between PKA and Akt pathways. In: Oncogene. 2009 ; Vol. 28, No. 32. pp. 2849-2859.
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