The colon mitosis-inhibitor pyroglutamyl-histidyl-glycine alters expression of immediate-early cancer-related genes in HT-29 cells

Anticancer Res. 2003 Mar-Apr;23(2B):1229-34.

Abstract

Background: The intestinal mitosis-inhibiting peptide pyroglu-His-GlyOH (pEHG), inhibits normal intestinal epithelial cells and the human colon adenocarcinoma cell line HT-29 and increases the expression of c-fos (1). In this study, we investigated the mechanisms of the growth-inhibiting effects of pEHG.

Materials and methods: cDNA expression array was hybridized with cDNA from HT-29 cells exposed to pEHG or control. The results were confirmed with Northern blot or real-time PCR.

Results: pEHG(1 nM) provoked a significant increase in the expression of the early growth response protein 1 (egr-1) after an incubation of 20 minutes, while c-fos was confirmed up-regulated by the same treatment. We further studied the expression of fosB, c-jun and junB, in the AP-1 complex. fosB was up-regulated 20-fold, but only minor effects on jun variants were observed.

Conclusion: pEHG stimulates the gene expression of some immediate-early transcription factors involved in cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / biosynthesis
  • Carcinoma / pathology*
  • Colonic Neoplasms / pathology*
  • DNA, Complementary / genetics
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, Immediate-Early / drug effects*
  • Genes, fos / drug effects
  • Genes, jun / drug effects
  • Growth Inhibitors / pharmacology*
  • Humans
  • Immediate-Early Proteins / biosynthesis*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Mitosis / drug effects
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Oligonucleotide Array Sequence Analysis
  • Oligopeptides / pharmacology*
  • Proto-Oncogene Proteins c-fos*
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Transcription Factor AP-1 / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics

Substances

  • Bacterial Proteins
  • DNA, Complementary
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • FOSB protein, human
  • Growth Inhibitors
  • Immediate-Early Proteins
  • Neoplasm Proteins
  • Oligopeptides
  • Proto-Oncogene Proteins c-fos
  • Proto-Oncogene Proteins c-jun
  • Transcription Factor AP-1
  • Transcription Factors
  • pyroglutamyl-histidyl-glycine
  • Pyrrolidonecarboxylic Acid