UMMS Affiliation

Department of Medicine, Division of Gastroenterology; Department of Cancer Biology

Publication Date

12-3-2005

Document Type

Article

Subjects

Animals; Antigens, CD95; Apoptosis; Helicobacter Infections; Helicobacter felis; Male; Mice; Mice, Inbred C57BL; Stomach Neoplasms

Disciplines

Cancer Biology | Gastroenterology

Abstract

The initiating molecular events in Helicobacter-induced gastric carcinogenesis are not known. Early in infection, Fas antigen-mediated apoptosis depletes parietal and chief cell populations, leading to architectural distortion. As infection progresses, metaplastic and dysplastic glands appear, which are resistant to Fas-mediated apoptosis. These abnormal lineages precede, and are thought to be the precursor lesions of, gastric cancer. Acquisition of an antiapoptotic phenotype before transformation of cells suggests that loss of Fas sensitivity may be an early required trait for gastric cancer. We reasoned that forced Fas-apoptosis resistance would result in earlier and more aggressive gastric cancer in our mouse model. Fas antigen-deficient (lpr) mice or C57BL/6 wild-type mice were irradiated and reconstituted with C57BL/6 marrow forming partial lpr/wt chimera or wt/wt control mice, extending the life span of the lpr and ensuring a competent immune response to Helicobacter felis infection. Infected lpr/wt mice developed gastric cancer as early as 7 months after infection (compared with 15 months in wt/wt mice). At 10 months (90%) and 15 months (100%), mice developed aggressive invasive lesions. This earlier onset and more aggressive histology strongly argues that Fas-apoptosis resistance is an early and important feature of gastric cancer formation.

Rights and Permissions

Citation: Cancer Res. 2005 Dec 1;65(23):10912-20. Link to article on publisher's site

DOI of Published Version

10.1158/0008-5472.CAN-05-1802

Related Resources

Link to article in PubMed

Journal/Book/Conference Title

Cancer research

PubMed ID

16322238

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