PP1, PKA and DARPP-32 in breast cancer: a retrospective assessment of protein and mRNA expression

Saidy, Behnaz; Kotecha, Shreeya; Butler, Anna; Rakha, Emad; Ellis, Ian; Green, Andrew; Martin, Stewart; Storr, Sarah

Abstract

Cyclic-AMP dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) are proteins involved in numerous essential signalling pathways that modulate physiological and pathological functions. Both PP1 and PKA can be inhibited by dopamine and cAMP regulated phosphoprotein 32kDa (DARPP-32). Using immunohistochemistry, PKA and PP1 expression was determined in a large primary breast tumour cohort to evaluate associations with clinical outcome and clinicopathological criteria (n>1100). In addition, mRNA expression of PKA and PP1 subunits was assessed in the METABRIC dataset (n=1980).
Low protein expression of PKA was significantly associated with adverse survival of breast cancer patients; interestingly, this relationship was stronger in ER positive breast cancer patients. PP1 protein expression was not associated with patient survival. PKA and PP1 subunit mRNA was also assessed; PPP1CA, PRKACG and PRKAR1B were associated with breast cancer specific survival.
In patients with high expression of DARPP-32, low expression of PP1 was associated with adverse survival when compared to high expression in the same group. PKA and PP1 expression are of significant interest in cancer as they are involved in a wide array of cellular processes and this data indicates PKA and PP1 may play an important role in patient outcome.

Citation

Saidy, B., Kotecha, S., Butler, A., Rakha, E., Ellis, I., Green, A., Martin, S., & Storr, S. (2021). PP1, PKA and DARPP-32 in breast cancer: a retrospective assessment of protein and mRNA expression. Journal of Cellular and Molecular Medicine, 25(11), 5015-5024. https://doi.org/10.1111/jcmm.16447

• Journal Article Type: Article
• Acceptance Date: Feb 24, 2021
• Online Publication Date: May 15, 2021
• Publication Date: 2021-06
• Deposit Date: Jun 22, 2021
• Publicly Available Date: Jun 25, 2021
• Journal: Journal of Cellular and Molecular Medicine
• Print ISSN: 1582-1838
• Electronic ISSN: 1582-4934
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 11
• Pages: 5015-5024
• DOI: https://doi.org/10.1111/jcmm.16447
• Public URL: https://nottingham-repository.worktribe.com/output/5361498
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16447