Cell cycle-dependent expression of p42.3 promotes mitotic progression in malignant transformed cells

Mol Carcinog. 2014 May;53(5):337-48. doi: 10.1002/mc.21982. Epub 2012 Nov 28.

Abstract

In an earlier study, we cloned the p42.3 gene and showed that its expression was specific to tumors in a number of tumor cell lines and primary tumor tissues. However, the biological role and function of this gene remains largely unknown. In this study, p42.3 expression was found to be cell cycle-dependent at both the mRNA and protein levels in several human tumor cell lines. Typically, abundant expression was detected at G1 and M phases compared with S and G2 phases. Expression peaked at early G1 phase then decreased drastically at late G1, S, and G2. Furthermore, transfection of the p42.3 gene into NIH3T3 cells promoted malignant transformation, accompanied by accelerated mitotic progression and altered chromosome segregation. It was also observed that Cyclin B1 was upregulated and Cdc2-Tyr15 was downregulated following p42.3 overexpression in NIH3T3 cells. Combined, these results indicate that p42.3 as a cell cycle-regulated gene contributes to promoting cell cycle progression through disruption of mitotic regulation, and may play important roles in malignant transformation.

Keywords: cell cycle; cell transformation; early G1; mitotic progression; p42.3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation*
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Fluorescence
  • Mitosis / physiology*
  • NIH 3T3 Cells
  • Nuclear Proteins
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • SAPCD2 protein, human