Enhanced expression of transcription factor E2F in Helicobacter pylori-infected gastric mucosa.
OBJECTIVE
Helicobacter pylori is implicated in gastric carcinogenesis through increased gastric epithelial cell turnover. In fact, high proportions of proliferating and apoptotic epithelial cells are found in H. pylori-infected gastric mucosa. E2F, a transcription factor, induces coordinated transactivation of a set of genes involved in cell cycle progression. The aim of this study was to investigate the expression of E2F in H. pylori-infected gastric mucosa and examine the correlation between such expression and gastric epithelial cell proliferation and apoptosis.


METHODS
Twenty-five patients with H. pylori-associated gastritis (HAG) and 13 control subjects negative for H. pylori were examined. E2F expression was studied in situ by Southwestern histochemistry, a method used to localize transcription factors. Labeled double-stranded oligo-DNA with specific consensus sequence for E2F binding sites was reacted with frozen sections from antral biopsy specimens obtained at endoscopy. Gastric epithelial cell proliferation was assessed by immunostaining of proliferating cell nuclear antigen (PCNA), while apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). The percentages of epithelial cells with nuclear staining for PCNA and E2F were expressed as a positivity index (PI). The percentage of TUNEL-positive epithelial cells was defined as apoptotic index.


RESULTS
E2F was expressed in the nuclei of gastric epithelial cells within gastric pits. E2F PI in H. pylori-infected gastric mucosa was significantly higher than that in noninfected. Expression of E2F correlated well with PCNA-positive epithelial cells. We also demonstrated colocalization of PCNA with E2F expression in the same epithelial cells. Apoptotic index was also high in H. pylori-infected mucosa, and correlated with E2F PI.


CONCLUSIONS
Our results demonstrated a significant increase in the expression of E2F in H. pylori-infected mucosa, which correlated with both the percentages of PCNA- and TUNEL-positive cells. Our results suggest that enhanced E2F expression in gastric mucosa may be involved in H. pylori-related gastric carcinogenesis through accelerated cell turnover.
Isomoto
Hajime
H
The Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Furusu
Hisashi
H
Shin
Masashi
M
Ohnita
Ken
K
Miyazaki
Masanobu
M
Omagari
Katsuhisa
K
Mizuta
Yohei
Y
Murase
Kunihiko
K
Inoue
Ken-ichiro
K
Murata
Ikuo
I
Koji
Takehiko
T
Kohno
Shigeru
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D016480:Helicobacter pylori; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008875:Middle Aged; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors