CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells

Oncol Rep. 2012 Apr;27(4):1266-76. doi: 10.3892/or.2011.1617. Epub 2011 Dec 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biliary Tract Neoplasms / enzymology*
  • Biliary Tract Neoplasms / genetics
  • Biliary Tract Neoplasms / mortality
  • Biliary Tract Neoplasms / pathology
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chi-Square Distribution
  • China
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Female
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins c-raf / metabolism
  • RNA Interference
  • Resting Phase, Cell Cycle / drug effects
  • Survival Analysis
  • Time Factors
  • Transfection
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-raf
  • CDK10 protein, human
  • Cyclin-Dependent Kinases