Overexpression of 14-3-3gamma causes polyploidization in H322 lung cancer cells

Mol Carcinog. 2007 Oct;46(10):847-56. doi: 10.1002/mc.20314.

Abstract

The 14-3-3 proteins are a family of highly conserved proteins that participate in a wide variety of cellular processes. Mounting evidence suggests that 14-3-3 proteins have a role in human cancers, however their role in tumorigenesis is unclear. Here we report that over-expression of 14-3-3 gamma protein in human lung cancer cell line H322 results in abnormal DNA replication and polyploidization. Cells that overexpress 14-3-3 gamma are resistant to microtubule inhibitors and can reenter the cell cycle in the absence of mitosis suggesting that elevated levels of 14-3-3 gamma may enable cells to bypass the mitotic checkpoint. Taken together, our data indicate that 14-3-3gamma may contribute to tumorigenesis by promoting genomic instability.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 14-3-3 Proteins / genetics*
  • Cell Cycle
  • DNA Replication
  • Humans
  • Lung Neoplasms / genetics*
  • Mitotic Index
  • Nocodazole / pharmacology
  • Polyploidy*
  • Protein Kinases / analysis
  • Tubulin Modulators / pharmacology
  • Tumor Cells, Cultured

Substances

  • 14-3-3 Proteins
  • Tubulin Modulators
  • Protein Kinases
  • histone H1 kinase
  • Nocodazole