CDK10 functions as a tumor suppressor gene and regulates survivability             of biliary tract cancer cells.
Cyclin-dependent kinase 10 (CDK10) is a member of the Cdc2 family of kinases,             and has been demonstrated to be an important determinant of resistance to endocrine             therapy for breast cancer. To investigate the expression and possible function             of CDK10 in biliary tract cancer (BTC), we systematically examined CDK10 in tissues             and cell lines. We found that expression of CDK10 was downregulated in both biliary             tract tumors and cell lines. Remarkably, the expression of CDK10 correlated with             clinical characteristics. Overexpression or knockdown of CDK10, respectively,             inhibited or promoted cell proliferation, colony formation and migration. This             suggests that CDK10 functions as a tumor suppressor gene in BTC. Overexpression             of CDK10 caused malignant cells to become sensitive to chemotherapy and other             hostile environments, suggesting that CDK10 functions to regulate survivability             of BTC cells. We investigated the expression of six genes to resolve the mechanism.             c-RAF was negatively regulated by CDK10 in both cells and specimens. Our results             indicate that CDK10 plays a crucial role in the growth and survivability of biliary             tract cancer, and offers a potential therapeutic target for this fatal disease.
Department of Hepato-pancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, PR China.
Jian-Hua
JH
Yu
Xiang-Yu
XY
Zhong
Wei-Guang
WG
Zhang
Zhi-Dong
ZD
Wang
Qin
Q
Dong
Sheng
S
Tai
Hui
H
Li
Yun-Fu
YF
Cui
D000970:Antineoplastic Agents / Q000494:pharmacology; D001661:Biliary Tract Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016009:Chi-Square Distribution; D002681:China; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D034622:RNA Interference; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016019:Survival Analysis; D013997:Time Factors; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins; D019908:Proto-Oncogene Proteins c-raf; C501013:CDK10 protein, human; D018844:Cyclin-Dependent Kinases