Clinical and biological significance of Cdk10 in hepatocellular carcinoma.
Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Xiang-yu
XY
Zhong
Xiao-xue
XX
Xu
Jian-hua
JH
Yu
Gui-xing
GX
Jiang
Yang
Y
Yu
Sheng
S
Tai
Zhi-dong
ZD
Wang
Yun-fu
YF
Cui
D000368:Aged; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology; D018844:Cyclin-Dependent Kinases / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015251:Epirubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005965:Glucuronates / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
D005965:Glucuronates; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C074868:epidoxorubicin glucuronide; D015251:Epirubicin; C501013:CDK10 protein, human; D018844:Cyclin-Dependent Kinases; D002945:Cisplatin