关键词：前列腺癌激素;磷酸酶;;蛋白质;行为;细胞(生物学);疾病;增长(生理学)
摘 要：Relapsed disease is highly aggressive and poses an increased risk of morbidity and death. Previously, we demonstrated that PPP2CA, which encodes the catalytic-subunit (alpha-isoform) of the protein phosphatase 2A (PP2AC ), is downregulated in CR PCa. The level of PP2AC was decreased in majority of CR PCa cell lines and cancer lesions as compared to the adjacent normal/benign tumor tissues. Under this project, we have utilized multiple approaches to demonstrate a functional role of PP2A in human prostate cancer progression. Specifically, we have generated and characterized stable PPP2CA overexpression (C4-2 and PC3) and knockdown (LNCaP) transfectants and obtained experimental evidence (in vitro) for the role of PP2A downregulation in growth, androgen depletion- resistance and aggressive behavior of prostate cancer cells. We have also developed in vivo experimental support for a suppressor role of PP2A in prostate cancer progression using orthotopic mouse model. Our data strongly suggest that downregulation of PP2A is associated with human prostate cancer progression and restoration of PP2A activity may be an effective approach for the treatment of the advanced disease.