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


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.


CONCLUSIONS
pEHG stimulates the gene expression of some immediate-early transcription factors involved in cell proliferation.
Reichelt
Wenche H
WH
Institute of Pediatric Research, University of Oslo, National Hospital, N-0027 Oslo, Norway. w.h.reichelt@klinmed.uio.no
Yndestad
Arne
A
Wright
Marianne S
MS
Elgjo
Kjell
K
Haug
Terje
T
Reichelt
Karl L
KL
D001426:Bacterial Proteins / Q000096:biosynthesis; D002277:Carcinoma / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D051766:Early Growth Response Protein 1; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017781:Genes, Immediate-Early / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects; D016758:Genes, jun / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D001426:Bacterial Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C064269:FOSB protein, human; D006131:Growth Inhibitors; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D009842:Oligopeptides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C023866:pyroglutamyl-histidyl-glycine; D011761:Pyrrolidonecarboxylic Acid