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PP1, PKA and DARPP-32 in breast cancer: A retrospective assessment of protein and mRNA expression |
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| Authors: | Behnaz Saidy Shreeya Kotecha Anna Butler Emad A Rakha Ian O Ellis Andrew R Green Stewart G Martin Sarah J Storr |
| Institution: | 1. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, Nottingham, UK
Contribution: Data curation (equal), Formal analysis (equal), ?Investigation (equal), Writing - review & editing (equal);2. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, Nottingham, UK Contribution: Data curation (equal), ?Investigation (equal), Writing - review & editing (equal);3. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, Nottingham, UK Contribution: Resources (equal), Writing - review & editing (equal);4. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, Nottingham, UK Contribution: Project administration (equal), Resources (equal), Supervision (equal), Writing - review & editing (equal);5. Division of Cancer and Stem Cells, Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, Nottingham, UK |
| 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 32 kD (DARPP-32). Using immunohistochemistry, PKA and PP1 expression was determined in a large primary breast tumour cohort to evaluate associations between clinical outcome and clinicopathological criteria (n > 1100). In addition, mRNA expression of PKA and PP1 subunits was assessed in the METABRIC data set (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 expression and PP1 expression are of significant interest in cancer as they are involved in a wide array of cellular processes, and these data indicate PKA and PP1 may play an important role in patient outcome. |
| Keywords: | DARPP-32 PKA PP-1 |