title: High expression of CDC6 is associated with accelerated cell proliferation and poor prognosis of epithelial ovarian cancer.
abstract: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with the oncogenic activities in human cancers, but the biological function and clinical significance of CDC6 in EOC remain unclear. The aim of the present study is to examine the effect of CDC6 on epithelial ovarian cancer (EOC) cells proliferation. We found that CDC6 protein level was up-regulated in EOC tissues compared with the normal ovary tissues. CDC6 expression correlated significantly with FIGO stage (p<0.001), differentiation grade (p=0.002), ascites (p<0.001), malignant tumor cells in ascites (p=0.004), and lymph node status (p<0.001). In vitro, after the release of ovarian cancer cell line (HO8910) from serum starvation, the expression of CDC6, cyclinD1, and PCNA was up-regulated, whereas p16 expression was down-regulated. Furthermore, down-regulation of CDC6 in HO8910 cells decreased cell proliferation and colony formation. HO8910 cells transfected with sh CDC6#1 underwent G1 phase cell cycle arrest. Collectively, this study provides a novel regulatory signaling pathway of CDC6-regulated EOC growth and a new potential therapeutic target for EOC patients.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Lifei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pathology, Nantong University Cancer Hospital, Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gynecologic Oncology, Nantong University Cancer Hospital, Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China.
authors.forename: Menghui
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China. Electronic address: ntfytch@163.com.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China. Electronic address: sumin_nt@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Su
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000401:mortality / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D014162:Transfection; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins
keywords: Cell division cycle 6 (CDC6); Cell proliferation; Epithelial ovarian cancer; Rb/p16 pathway; Therapeutic target