Reduction in alkaline sphingomyelinase in colorectal tumorigenesis is not related to the APC gene mutation.
OBJECTIVE
The sphingomyelin pathway is an important intracellular mechanism in regulating cell growth. The first step in this pathway is catalysed by sphingomyelinases. Alkaline sphingomyelinase is specifically located in the intestinal tract. Markedly reduced alkaline sphingomyelinase activities have been found in sporadic colorectal tumours and in familial adenomatous polyposis adenomas. Since the adenomatous polyposis coli (APC) gene is mutated in about 80% of sporadic colorectal tumors, and familial adenomatous polyposis is the consequence of a germline mutation of the same gene, we examined whether low alkaline sphingomyelinase activity is linked to APC gene mutations.


METHODS
Both germline and sporadic adenomatous polyposis coli gene mutations were studied. Alkaline, neutral, and acid sphingomyelinase activities were measured in the intestinal mucosa and content of multiple intestinal neoplasia mice, a murine model of familial adenomatous polyposis and compared to control mice. Alkaline sphingomyelinase activity was also measured in 11 human rectal tumors with APC gene mutation and compared with 9 control tumors without mutation.


RESULTS
Alkaline, neutral, and acid sphingomyelinase activities were present in the small intestine and colon in both mice types with no differences in hydrolytic capacity or distribution pattern. In sporadic rectal tumors similar alkaline sphingomyelinase activities were identified in tumors with somatic APC gene mutations as in samples without mutations. In the tumors without detectable APC mutations beta-catenin was analyzed, but no mutation was detected.


CONCLUSIONS
Alkaline sphingomyelinase is not directly linked to adenomatous polyposis coli gene mutations.
Hertervig
Erik
E
Department of Medicine, Lund University Hospital, 22185, Lund, Sweden. erik.hertervig@med.lu.se
Nilsson
Ake
A
Nilbert
Mef
M
Duan
Rui-Dong
RD
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000503:physiopathology*; D000328:Adult; D000368:Aged; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003106:Colon / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000503:physiopathology*; D004252:DNA Mutational Analysis; D004195:Disease Models, Animal; D005260:Female; D017491:Genes, APC; D018095:Germ-Line Mutation; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology*
D013108:Sphingomyelin Phosphodiesterase