Reduction of gap junction protein connexin 32 in rat atrophic gastric mucosa as an early event in carcinogenesis.
This study was conducted to examine the possible relationship among connexin 32 (Cx32) expression, cell proliferation and differentiation in the normal stomach, N-methyl-N'-nitro-nitrosoguanidine (MNNG)-induced atrophic gastritis, and carcinoma in rats. Atrophic gastritis and adenocarcinoma were induced by the administration of MNNG for 8 and 30 weeks, respectively. Cell proliferation was detected by staining with 5-bromo-2'-deoxyuridine (BrdU). The proliferative zone (BrdU-positive zone), located in the lower third of the gastric gland in controls, was elongated in atrophic gastritis. In adenocarcinoma, BrdU-positive cells were distributed diffusely. Cx32 expression was investigated by an indirect immunofluorescence method. In both control and atrophic gastritis specimens, Cx32 fluorescence was abundant in the surface epithelium, but was rarely detected in the glandular portion or the proliferative zone. The length of the Cx32-positive mucosa was significantly less than the control value in atrophic gastritis and no such positive mucosa was visible in adenocarcinoma. The results of this study indicate that the loss of cell-cell communication through the gap junction, associated with elongation of the proliferative cell zone, may be manifested much earlier than carcinoma. We regard this model as useful for investigating the development of atrophic gastritis into gastric carcinoma.
Nagahara
A
A
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Watanabe
S
S
Miwa
H
H
Endo
K
K
Hirose
M
M
Sato
N
N
D000230:Adenocarcinoma / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D000818:Animals; D002273:Carcinogens; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D017630:Connexins / Q000378:metabolism*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005757:Gastritis, Atrophic / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D008769:Methylnitronitrosoguanidine; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D000097002:Gap Junction beta-1 Protein
D002273:Carcinogens; D017630:Connexins; D008769:Methylnitronitrosoguanidine; D000097002:Gap Junction beta-1 Protein