Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer

Cancer Biol Ther. 2014 Sep;15(9):1268-79. doi: 10.4161/cbt.29691. Epub 2014 Jun 27.

Abstract

The high morbidity and mortality of colorectal cancer pose a significant public health problem worldwide. Here we assessed the pro-cancer efficacy and mechanism of action of CCNB1 in different colorectal cancer cells. We provided evidence that CCNB1 mRNA and protein level were upregulated in a subset of human colorectal tumors, and positively correlated with Chk1 expression. Repression of Chk1 caused a significant decrease in cell proliferation and CCNB1 protein expression in colorectal cancer cells. Furthermore, downregulation of CCNB1 impaired colorectal cancer proliferation in vitro and tumor growth in vivo. Specifically, suppression of CCNB1 caused a strong G 2/M phase arrest in both HCT116 and SW480 cells, interfering with the expression of cdc25c and CDK1. Additionally, CCNB1 inhibition induced apoptotic death in certain colorectal cancer cells. Together, these results suggest that CCNB1 is activated by Chk1, exerts its oncogenic role in colorectal cancer cells, and may play a key role in the development of a novel therapeutic approach against colorectal cancer.

Keywords: CCNB1; Chk1; apoptosis; cell cycle; cell growth; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • CDC2 Protein Kinase
  • Cell Line, Tumor
  • Cell Proliferation
  • Checkpoint Kinase 1
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism*
  • Cyclin-Dependent Kinases / metabolism
  • Down-Regulation
  • G2 Phase Cell Cycle Checkpoints
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • M Phase Cell Cycle Checkpoints
  • Mice, Inbred BALB C
  • Mice, Nude
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • cdc25 Phosphatases / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • CCNB1 protein, human
  • Cyclin B1
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Chek1 protein, mouse
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • CDC25C protein, human
  • cdc25 Phosphatases