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Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation

J L Cmarik1, H Min, G Hegamyer

  • 1Basic Research Laboratory, Frederick Cancer Research and Development Center, National Cancer Institute, Frederick, MD 21702, USA. cmarik@ncifcrf.gov

Proceedings of the National Academy of Sciences of the United States of America
|November 26, 1999
PubMed

Insights

The Pdcd4 protein inhibits neoplastic transformation by preventing tumor promoter-induced changes in cells. Reduced Pdcd4 levels lead to a transformation-sensitive phenotype, while its overexpression restores resistance.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell biology

Background:

  • JB6 cells are mouse epidermal cells used to study neoplastic transformation.
  • Promotion-sensitive (P+) cells transform in response to tumor promoters, unlike promotion-resistant (P-) cells.

Purpose of the Study:

  • To identify novel genes involved in inhibiting neoplastic transformation.
  • To investigate the function of the Pdcd4 gene product in cellular transformation.

Main Methods:

  • Differential display screening of mouse JB6 P+ and P- cells.
  • cDNA isolation and sequencing of a differentially expressed gene fragment (A7-1).
  • Generation of stable cell lines expressing antisense Pdcd4 and sense Pdcd4 fragments.

Main Results:

  • A novel gene product, Pdcd4 (Programmed Cell Death 4), was identified and found to be highly expressed in P- cells.
  • Pdcd4 protein levels correlated with mRNA expression, being higher in P- cells.
  • Reducing Pdcd4 levels in P- cells induced a P+ phenotype, while restoring Pdcd4 expression reverted cells to a P- phenotype.

Conclusions:

  • The Pdcd4 protein functions as a critical inhibitor of neoplastic transformation.
  • Pdcd4 plays a significant role in determining cellular sensitivity or resistance to tumor promoters.

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