The human tumor suppressor CEACAM1 modulates apoptosis and is implicated in early colorectal tumorigenesis.
Defects in the adenomatous polyposis coli (APC) tumor suppressor pathway are sufficient for neoplastic transformation as the initiating step in colorectal carcinogenesis. In contrast, hyperplastic tumors possess normal APC function, and it is unclear whether they represent significant precursor lesion in cancer development. CEACAM1 is a tumor suppressor whose expression is known to be lost in the great majority of early adenomas and carcinomas. We found that loss of CEACAM1 expression is more common in neoplastic tumors than APC mutations. While APC function was normal in hyperplastic aberrant cypt foci and hyperplastic polyps, loss of CEACAM1 was observed as frequently as in the neoplasias. Moreover, the presence or absence of CEACAM1 expression in the hyperplastic tumors correlates with normal or reduced apoptosis, respectively. In vitro, CEACAM1 acts as a regulator of apoptosis in CEACAM1-transfected Jurkat cells. Finally, in human HT29 colon cancer cells, apoptosis can be specifically restored by induction of CEACAM1 expression. These data suggest an oncodevelopmental link between neoplasia and hyperplasia and demonstrate that CEACAM1 acts as a regulator of apoptosis in the colonic epithelium. Thus, failure of the maturing colon cell to express CEACAM1 is likely to contribute to the development of hyperplastic lesions, which may eventually pave the way to neoplastic transformation and colon cancer development.
Nittka
Stefanie
S
Institute for Clinical Chemistry, Medical Faculty Mannheim of the University of Heidelberg, D-68167 Mannheim, Germany.
Günther
Juliane
J
Ebisch
Cornelia
C
Erbersdobler
Andreas
A
Neumaier
Michael
M
D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015815:Cell Adhesion Molecules; D015179:Colorectal Neoplasms / Q000235:genetics / Q000503:physiopathology*; D017931:DNA Primers; D017491:Genes, APC; D016147:Genes, Tumor Suppressor; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation
D015703:Antigens, CD; D000943:Antigens, Differentiation; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D017931:DNA Primers