期刊
ONCOGENE
卷 24, 期 42, 页码 6450-6458出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1208791
关键词
APC; PLA2; phospholipase; Mom1; intestine; cancer; mouse; BODIPY
资金
- NCI NIH HHS [P01CA72027, P01 CA072027, R01 CA089560, R01 CA89560] Funding Source: Medline
- NIDDK NIH HHS [R01 DK060369] Funding Source: Medline
- NINDS NIH HHS [F32 NS010326] Funding Source: Medline
The secreted phospholipase A(2) type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. To determine if intestinal secreted phospholipase A(2) (sPLA(2)) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPL2 activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA(2) enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA(2)-IIA gene sequence in inbred strains, we detected low levels of enzyme activity in inbred strains containing sPLA(2)-IIA mutations; these strains were also associated with greater numbers of intestinal polyps. Additionally, the assay was able to distinguish differences in levels of sPLA(2) activity between neoplasia-resistant strains, which were then shown by sequencing to carry variant wild-type sPLA(2)-IIA alleles. Immunohistochemical analyses of intestinal tissues were consistent with sPLA(2)-IIA activity levels. This approach enables further studies of the mechanisms of sPLA(2) action influencing the development and tumorigenesis of the small intestine and colon in both mice and humans.
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