Abstract P2-26-11: Protein phosphatase 1 catalytic units, PPP1CA, PPP1CB and PPP1CC in breast cancer

Abstract

Abstract Introduction. Protein phosphatase-1 (PP1) belongs to the Serine/threonine-protein phosphatase family and is known to participate in multiple functions in the cells including glycogen metabolism, cellular proliferation and cell receptor regulations. Protein phosphtase-1 has three catalytic units, namely PPP1CA, PPP1CB and PPP1CC. A PP1 protein complex is composed of one of the catalytic units and at least of one the various phosphatase regulatory units (PPP1Rs). The regulatory units of the phosphatase, abundant in numbers, also influence the functions of the protein phosphatase within cells. PP1 has been indicated to have a role in certain clinical conditions such as the Alzheimer’s and certain viral infections. The value of the PP1 catalytic units in clinical cancers including breast cancer is not well established, therefor this current study aimed to examine the expression profile of the three PP1 catalytic units in human breast cancer and attempted to establish the clinical relevance of the catalytic units in the disease progression of breast cancer. Methods. Fresh frozen normal mammary tissues and breast cancer tissues were investigated for the levels of gene transcripts of the three PP1 catalytic units were quantified and corrected with an epithelial cell marker. The expression and integrated expression profile of PPP1A, PPP1B and PPP1C in the tissues were assessed against the pathological, clinical and outcome of the patients as well as the hormone receptor status. Results. All three catalytic units of PP1 were positively expressed in normal and tumour breast tissues, with PPP1A at significantly higher levels in normal mammary tissues than tumours (p=0.01) and PPP1B and PPP1C showing no significant difference. Expression of PPP1B in breast cancer was significantly lower in high grade breast cancers (p< 0.05 vs low grade), in tumours from patients who died of breast cancer (p=0.047 vs those who survived) and with breast cancer related incidence (p=0.048 vs incidence free). The most significant finding of the present study was a correlation between high levels of all three catalytic units and favourable overall survival of the patients. Those patients with high levels of PPP1A, PPP1B and PPP1C in breast tumours had a mean survival time of 142.6, 141.6 and 140.3 months compared with those with low levels respectively at 111.8, 115.8 and 117.6 months. When the expression profiles of the three units were integrated, the integrated profile formed a highly valuable and independent indicator for both overall survival (p=0.008, HR=0.694) and for disease free survival (p=0.004, HR=0.702). The predictive value of PPP1A/PPP1B/PPP1C for survival was more significant for ER negative tumours than ER positive tumours (p=0.003), but appeared to be indifferent for Her2 status. Finally, our data indicated that the integrated expression of the three catalytic units had a significant predictive value in bone metastasis of the patients (p=0.008, HR=0.546). Discussion. Protein phosphatase-1 catalytic units, PPP1CA, PPP1CB and PPP1CC are expressed in human mammary tissues; raised levels of the catalytic units are a favourable clinical indicator for the survival of patients and for a decreased tendency to develop bone metastasis. Citation Format: Xuefei Dong, Tracey A. Martin, QingPing Dou, Wen G. Jiang, Eleri Davies. Protein phosphatase 1 catalytic units, PPP1CA, PPP1CB and PPP1CC in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-26-11.