The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin-induced intestinal neoplasia.
Mutations in the APC gene are responsible for various familial and sporadic colorectal cancers. Min mice carry a dominant mutation in the homolog of the Apc gene and develop multiple adenomas throughout their small and large intestine. Quantitative trait loci studies have identified a locus, Mom1, which maps to the distal region of chromosome 4, that dramatically modifies Min-induced tumor number. We report here the identification of a candidate gene for Mom1. The gene for secretory type II phospholipase A2 (Pla2s) maps to the same region that contains Mom1 and displays 100% concordance between allele type and tumor susceptibility. Expression and sequence analysis revealed that Mom1 susceptible strains are most likely null for Pla2s activity. Our results indicate that Pla2s acts as a novel gene that modifies polyp number by altering the cellular microenvironment within the intestinal crypt.
MacPhee
M
M
Department of Microbiology and Immunology, Jefferson Cancer Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Chepenik
K P
KP
Liddell
R A
RA
Nelson
K K
KK
Siracusa
L D
LD
Buchberg
A M
AM
D011125:Adenomatous Polyposis Coli / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D017491:Genes, APC; D005799:Genes, Dominant; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008817:Mice, Mutant Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009115:Muridae; D009154:Mutation; D010741:Phospholipases A / Q000235:genetics* / Q000502:physiology; D054467:Phospholipases A2; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats
D018076:DNA, Complementary; D010741:Phospholipases A; D054467:Phospholipases A2