Publication: Immunohistochemical evidence for an impairment of autophagy in tumorigenesis of gastric carcinoids and adenocarcinomas in rodent models and patients
Authors
Vigen, Reidar Alexander ; Kodama, Yosuke ; Viset, Trond ; Fossmark, Reidar ; Waldum, Helge ; Kidd, Mark ; Wang, Timothy C. ; Modlin, Irvin M. ; Chen, Duan ; Zhao, Chun-Mei
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
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DOI
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info:eu-repo/semantics/article
Description
Abstract
Background/Aim: Autophagy has dual roles
in tumorigenesis: tumor-promoting or tumorsuppressing.
The aim of the present study was to
examine autophagy-related markers by immunohistochemistry
in gastric carcinoids and adenocarcinomas in
rodent models and patients.
Methods: Gastric carcinoids in Mastomys were
induced by loxtidine treatment. Spontaneously
developed gastric adenocarcinomas in Japanese cotton
rats and INS-GAS transgenic mice were included.
Patient tissue samples of gastric carcinoids or
adenocarcinomas were collected. Immunohistochemistry
was performed against autophagy-related gene protein-6
(ATG-6, also called beclin-1), ATG-5 and ATG-16.
Results: In tumor-free Mastomys, ATG-5, ATG-16
and beclin-1 were immunepositive in the gastric mucosa.
In tumor-bearing Mastomys, ATG-5 and ATG-16 were
negative in the tumors, whereas beclin-1 was positive in
four of five animals. In carcinoid patients, ATG-5 was
negative in six of ten, ATG-16 negative in nine of ten,
and beclin-1 negative in three of ten patients. In cotton
rats, ATG-5 and ATG-16 were negative in all tumors.
Beclin-1 was negative in three of five rats. In INS-GAS
mice, ATG-5 and beclin-1 were positive in the tumor
area, but the numbers of immunopositive cells per gland
were reduced by about 50% in comparison with wildtype
mice. In adenocarcinoma patients, ATG-5 and
ATG-16 were negative in eight of ten, and beclin-1
positive in all ten patients.
Conclusions: An impaired autophagy took place at
the stage of formation of ATG-5-ATG-12-ATG-16
complex in both gastric carcinoids and adenocarcinoma
of both rodent models and patients. ATG-5 and ATG-16
might be better markers than beclin-1 in assessing
autophagy in these lesions.
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Citation
Histology and histopathology, Vol. 28, n.º 4 (2013)
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