CCAAT enhancer binding protein β promotes tumor growth and inhibits apoptosis in prostate cancer by methylating estrogen receptor β

Dong Li, Jiumin Liu, Shang Huang, Xuecheng Bi, Baojun Wang, Qingke Chen, Hanzhong Chen,  Xiaoyong Pu

Abstract:

The CCAAT enhancer binding protein β (C/EBPβ) is overexpressed at late stages in carcinogenesis of prostate cancer (PCa), suggesting that it could potentially contribute to progression of PCa. Estrogen receptor beta (ERβ) is a tumor suppressor gene in PCa. However, whether C/EBPβ could regulate ERβ by promoter methylation is still poorly understood. In this study, expression levels of C/EBPβ and ERβ in two PC lines (LNCap and PC-3), prostatic epithelial cell line (RWPE-1), forty-eight paired noncancerous and cancerous peripheral blood samples were examined via qRT-PCR, western blotting and methylation-specific PCR. In addition, PCa cell line was infected with pCDH-C/EBPβ and pLKO.1-C/EBPβ and expression levels of C/EBPβ, ERβ and DNA methyltransferases were detected. Finally, the roles of C/EBPβ in proliferation and apoptosis of PCa cell line were examined by MTT and flow cytometer assay. Our results showed the higher frequency of promoter methylation of ERβ levels in blood samples from PCa patients (16 of 48 cases) compared with that from healthy controls (3 of 48). Besides, elevated expression levels of C/EBPβ were found in PCa patients and two PC lines (LNCap and PC-3) than noncancerous cases or prostatic epithelial cell line (RWPE-1), while opposite expression levels of ERβ were found. Overexpression of C/EBPβ could regulate ERβ expression, DNA methyltransferases expression, cell proliferation and apoptosis. Our results support the conclusion that C/EBPβ down-regulated ERβ expression through increasing its promoter methylation, and then regulateing proliferation and apoptosis in PCa.