title: Cell cycle-related kinase supports ovarian carcinoma cell proliferation via regulation of cyclin D1 and is a predictor of outcome in patients with ovarian carcinoma.
abstract: Our previous study has suggested that the cell cycle-related kinase (CCRK) is a putative candidate oncogene in glioblastoma tumorigenesis. The potential oncogenic role of CCRK and its clinical/prognostic significance, however, in ovarian carcinoma are unclear. In this study, CCRK expression was examined by immunohistochemistry in a series of ovarian carcinoma tissues. Overexpression of CCRK was detected in 53% of the ovarian carcinomas, and it was positively correlated with an ascending histological grade and/or advanced clinical stage of the disease (p < 0.05). In addition, overexpression of CCRK in ovarian carcinoma was determined to be a strong and an independent predictor of short overall survival (p < 0.05). In ovarian carcinoma cells, CCRK knockdown by RNAi led to a G1 phase cell cycle arrest, while CCRK overexpression by stable transfection of CCRK-containing plasmid pcDNA-CCRK promoted cell proliferation in vitro and tumor growth in vivo. In addition, CCRK knockdown was found to reduce cyclin D1 expression. Consistently, CCRK overexpression increased cyclin D1 expression, and furthermore, a significant correlation between expression of CCRK and cyclin D1 in ovarian carcinomas was observed (p < 0.001). These findings suggest a potential important role of CCRK in the control of cell proliferation via regulation of cyclin D1 expression, and the overexpression of CCRK, as detected by immunohistochemistry, is an independent molecular marker for shortened survival time of patients with ovarian carcinoma.
authors: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors: Guo-Qing
authors: GQ
authors: Wu
authors: Dan
authors: D
authors: Xie
authors: Guo-Feng
authors: GF
authors: Yang
authors: Yi-Ji
authors: YJ
authors: Liao
authors: Shi-Juan
authors: SJ
authors: Mai
authors: Hai-Xia
authors: HX
authors: Deng
authors: Johnny
authors: J
authors: Sze
authors: Xin-Yuan
authors: XY
authors: Guan
authors: Yi-Xin
authors: YX
authors: Zeng
authors: Marie C
authors: MC
authors: Lin
authors: Hsiang-Fu
authors: HF
authors: Kung
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D015331:Cohort Studies; D019938:Cyclin D1 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D014407:Tumor Cells, Cultured; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: C530104:CCND1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019938:Cyclin D1; D018844:Cyclin-Dependent Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase