Activation of Wnt signaling in the intestinal mucosa of Apc +/min mice does not cause overexpression of the receptor tyrosine kinase Met.
The receptor tyrosine kinase MET is overexpressed in human colorectal adenomas and carcinomas, suggesting an instrumental role for MET signaling in the onset and progression of colorectal cancer. To corroborate this role, animal models are needed. To study the expression of Met in the normal and neoplastic mouse intestine, we generated an Armenian hamster monoclonal antibody against mouse Met. By using this antibody in immunohistochemical studies, we observed strong Met expression in fetal mouse intestinal epithelial cells. In contrast, in the intestines of adult mice, Met expression was very low whereas the protein was undetectable on the neoplastic epithelium of intestinal adenomas in Apc+/min mice. By immunoblotting, we were also unable to detect Met in intestinal adenomas, whereas Met mRNA levels in microdissected adenomas were very low. The absence of detectable Met protein expression in adenomas of Apc+/min mice contrasts sharply with the vast overexpression of the protein in adenomas of humans with familial adenomatous polyposis or sporadic colorectal carcinomas. Our results imply that deregulation of Wnt signaling in mouse--unlike in human--intestinal epithelium does not result in Met overexpression. Our findings thus reveal important interspecies differences in the regulation of Met expression during intestinal tumorigenesis.
Boon
Elles M J
EM
Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands.
Pouwels
Walter
W
Redeker
Sandra
S
Joosten
Sander P J
SP
Hamann
Jörg
J
van der Neut
Ronald
R
Pals
Steven T
ST
D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D000818:Animals; D000911:Antibodies, Monoclonal; D006224:Cricetinae; D006801:Humans; D007120:Immunochemistry; D007413:Intestinal Mucosa / Q000737:chemistry / Q000196:embryology / Q000201:enzymology*; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000201:enzymology*; D051379:Mice; D008817:Mice, Mutant Strains; D042282:Microdissection; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
D025601:Adenomatous Polyposis Coli Protein; D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D051153:Wnt Proteins; D019859:Proto-Oncogene Proteins c-met; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases