Type 10 Soluble Adenylyl Cyclase is Overexpressed in Prostate Carcinoma and Controls Proliferation of Prostate Cancer Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2012 Dec 21

PMID 23255611

Citations 29

Authors

Jan-Paul Flacke

Hanna Flacke

Avinash Appukuttan

Rein-Juri Palisaar

Joachim Noldus

Brian D Robinson

H Peter Reusch

Jonathan H Zippin

Yury Ladilov

Affiliations

Soon will be listed here.

Abstract

cAMP signaling plays an essential role in modulating the proliferation of different cell types, including cancer cells. Until now, the regulation of this pathway was restricted to the transmembrane class of adenylyl cyclases. In this study, significant overexpression of soluble adenylyl cyclase (sAC), an alternative source of cAMP, was found in human prostate carcinoma, and therefore, the contribution of this cyclase was investigated in the prostate carcinoma cell lines LNCaP and PC3. Suppression of sAC activity by treatment with the sAC-specific inhibitor KH7 or by sAC-specific knockdown mediated by siRNA or shRNA transfection prevented the proliferation of prostate carcinoma cells, led to lactate dehydrogenase release, and induced apoptosis. Cell cycle analysis revealed a significant rise in the G(2) phase population 12 h after sAC inhibition, which was accompanied by the down-regulation of cyclin B(1) and CDK1. sAC-dependent regulation of proliferation involves the EPAC/Rap1/B-Raf signaling pathway. In contrast, protein kinase A does not play a role. In conclusion, this study suggests a novel sAC-dependent signaling pathway that controls the proliferation of prostate carcinoma cells.

Citing Articles

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