title: The Silencing of CCND2 by Promoter Aberrant Methylation in Renal Cell Cancer and Analysis of the Correlation between CCND2 Methylation Status and Clinical Features.
abstract: Cyclin D2 (CCND2) is a member of the D-type cyclins, which plays a pivotal role in cell cycle regulation, differentiation and malignant transformation. However, its expression status and relative regulation mechanism remains unclear in renal cell cancer (RCC). In our study, the mRNA expression level of CCND2 is down-regulated in 22/23 paired RCC tissues (p<0.05). In addition, its protein expression level is also decreased in 43/43 RCC tumor tissues compared with its corresponding non-malignant tissues (p<0.001). We further detected that CCND2 was down-regulated or silenced in 6/7 RCC cell lines, but expressed in "normal" human proximal tubular (HK-2) cell line. Subsequently, MSP and BGS results showed that the methylation status in CCND2 promoter region is closely associated with its expression level in RCC cell lines. Treatment with 5-Aza with or without TSA restored CCND2 expression in several methylated RCC cell lines. Among the 102 RCC tumors, methylation of CCND2 was detected in 29/102 (28%) cases. Only 2/23 (8.7%) adjacent non-malignant tissues showed methylation. We then analyzed the correlation of clinical features and its promoter methylation. Collectively, our data suggested that loss of CCND2 expression is closely associated with the promoter aberrant methylation.
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Lu
authors: L
authors: Wang
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.|Urogenital diseases (male) molecular diagnosis and treatment center, Beijing, 100034, China.
authors: Yun
authors: Y
authors: Cui
authors: National Research Center for Genitourinary Oncology, Beijing, 100034, China.
authors: Lian
authors: L
authors: Zhang
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Jindong
authors: J
authors: Sheng
authors: National Urological Cancer Center, Beijing, 100034, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Guanyu
authors: G
authors: Kuang
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Yu
authors: Y
authors: Fan
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Qian
authors: Q
authors: Zhang
authors: Department of Urology, Peking University First Hospital and Institute of Urology, Peking University, Beijing, 100034, China.
authors: Jie
authors: J
authors: Jin
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056742:Cyclin D2 / Q000235:genetics*; D019175:DNA Methylation; D020868:Gene Silencing; D016678:Genome; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D011401:Promoter Regions, Genetic
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2