Overcoming Fas-mediated apoptosis accelerates Helicobacter-induced gastric cancer in mice
Authors
Cai, XunStoicov, Calin
Li, Hanchen
Carlson, Jane E.
Whary, Mark T.
Fox, James G.
Houghton, JeanMarie
UMass Chan Affiliations
Department of Cancer BiologyDepartment of Medicine, Division of Gastroenterology
Document Type
Journal ArticlePublication Date
2005-12-03Keywords
AnimalsAntigens, CD95
Apoptosis
Helicobacter Infections
Helicobacter felis
Male
Mice
Mice, Inbred C57BL
Stomach Neoplasms
Cancer Biology
Gastroenterology
Metadata
Show full item recordAbstract
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.Source
Cancer Res. 2005 Dec 1;65(23):10912-20. Link to article on publisher's siteDOI
10.1158/0008-5472.CAN-05-1802Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40677PubMed ID
16322238Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-05-1802