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Dopamine and cAMP?regulated phosphoprotein 32kDa (DARPP?32), protein phosphatase?1 and cyclin?dependent kinase 5 expression in ovarian cancer

Martin, Stewart G.; Zhang, Siwei; Yang, Song; Saidy, Behnaz; Deen, Suha; Storr, Sarah J.

Dopamine and cAMP?regulated phosphoprotein 32kDa (DARPP?32), protein phosphatase?1 and cyclin?dependent kinase 5 expression in ovarian cancer Thumbnail


Authors

STEWART MARTIN STEWART.MARTIN@NOTTINGHAM.AC.UK
Professor of Cancer and Radiation Biology

Siwei Zhang

Song Yang

Behnaz Saidy

Suha Deen

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SARAH STORR sarah.storr@nottingham.ac.uk
Assistant Professor



Abstract

Dopamine and cyclic?AMP activated phosphoprotein Mr32kDa (DARPP?32) is a central signalling protein in neurotransmission. Following DARPP?32 phosphorylation by protein kinase A (PKA), DARPP?32 becomes a potent protein phosphatase 1 (PP1) inhibitor. DARPP?32 can itself inhibit PKA following DARPP?32 phosphorylation by cyclin?dependent kinase 5 (Cdk5). Increasing evidence indicates a role for DARPP?32 and its associated signalling pathways in cancer; however, its role in ovarian cancer remains unclear. Using immunohistochemistry, expression of DARPP?32, PP1 and Cdk5 was determined in a large cohort of primary tumours from ovarian cancer patients (n = 428, 445 and 434 respectively) to evaluate associations between clinical outcome and clinicopathological criteria. Low cytoplasmic and nuclear DARPP?32 expression was associated with shorter patient overall survival and progression?free survival (P = .001, .001, .004 and .037 respectively). Low nuclear and cytoplasmic DARPP?32 expression remained significantly associated with overall survival in multivariate Cox regression (P = .045, hazard ratio (HR) = 0.734, 95% confidence interval (CI) = 0.542?0.993 and P = .001, HR = 0.494, 95% CI = 0.325?0.749, respectively). High cytoplasmic and nuclear PP1 expression was associated with shorter patient overall survival and high cytoplasmic PP1 expression with shorter progression?free survival (P = .005, .033, and .037, respectively). High Cdk5 expression was associated with shorter progression?free survival (P = .006). These data suggest a role for DARPP?32 and associated signalling kinases as prognostic markers with clinical utility in ovarian cancer.

Citation

Martin, S. G., Zhang, S., Yang, S., Saidy, B., Deen, S., & Storr, S. J. (2020). Dopamine and cAMP?regulated phosphoprotein 32kDa (DARPP?32), protein phosphatase?1 and cyclin?dependent kinase 5 expression in ovarian cancer. Journal of Cellular and Molecular Medicine, 24(16), 9165-9175. https://doi.org/10.1111/jcmm.15553

Journal Article Type Article
Acceptance Date Jun 7, 2020
Online Publication Date Jun 25, 2020
Publication Date 2020-08
Deposit Date Oct 12, 2020
Publicly Available Date Mar 28, 2024
Journal Journal of Cellular and Molecular Medicine
Print ISSN 1582-1838
Electronic ISSN 1582-4934
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 24
Issue 16
Pages 9165-9175
DOI https://doi.org/10.1111/jcmm.15553
Keywords Molecular Medicine; Cell Biology
Public URL https://nottingham-repository.worktribe.com/output/4736754
Publisher URL https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.15553