Gene regulation and genetic susceptibility to neoplastic transformation: AP-1 and p80 expression in JB6 cells

Environ Health Perspect. 1991 Jun;93:111-9. doi: 10.1289/ehp.9193111.

Abstract

The mouse epidermal JB6 cell system consists of clonal genetic variants that are sensitive (P+) or resistant (P-) to the promotion of neoplastic transformation by phorbol esters and other tumor-promoting agents. P+ cells display AP-1-dependent phorbol-ester-inducible transactivation of gene expression, whereas P- cells have a defect in transactivation. Transfection of promotion sensitivity gene pro-1 into P- cells reconstituted both P+ phenotype and AP-1-dependent phorbol-ester-inducible transactivation. P- and P+ cells exhibited induction of c-jun and c-fos messenger RNA levels by phorbol ester, but P- cells had significantly lower basal and induced levels of jun mRNA than P+ cells. Basal and induced levels of c-jun protein were significantly lower in P- cells as well. Differences in levels the 80-kDa pI 4.5 protein p80 were also observed in JB6 cells as a function of preneoplastic progression; high levels of p80 protein and mRNA were observed in P- cells, intermediate levels in P+ cells, and negligible levels were observed in transformed derivatives of JB6 cells. Phorbol ester treatment induced phosphorylation but not synthesis of p80. These data are consistent with the hypotheses that AP-1 is required in the signal transduction pathway for promotion of neoplastic transformation by tumor promoter, that pro genes may control AP-1 activity, that threshold levels of Jun mRNA and protein may play a role in transactivation and promotion sensitivity, and that the p80 protein in JB6 cells may behave in vivo as a suppressor of cellular transformation.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carcinogens / pharmacology
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic / chemically induced
  • Cell Transformation, Neoplastic / genetics*
  • Clone Cells / drug effects
  • Clone Cells / pathology
  • Enhancer Elements, Genetic
  • Epidermal Cells*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genetic Predisposition to Disease
  • Mice
  • Mice, Inbred BALB C / genetics
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Phosphorylation
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Proto-Oncogene Proteins c-jun / genetics*
  • Proto-Oncogene Proteins c-jun / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Recombinant Fusion Proteins / biosynthesis
  • Transcriptional Activation / drug effects

Substances

  • Carcinogens
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • protein p80