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Title

Diversity in Secreted PLA2-IIA Activity Among Inbred Mouse Strains that are Resistant or Susceptible to ApcMin/+ Tumorigenesis

Authors

Marina Markova
Revati A. Koratkar
Karen A. Silverman
Vincent E. Sollars, Marshall University
Melina MacPhee-Pellini
Rhonda Walters
Juan P. Palazzo
Arthur M. Buchberg
Linda D. Siracusa
Steven A. Farber

Document Type

Article

Publication Date

9-22-2005

Abstract

The secreted phospholipase A₂ type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in Apc^Min/+ mice. To determine if intestinal secreted phospholipase A₂ (sPLA₂) activity was also attenuated in susceptible strains, we developed a sensitive assay to directly quantitate sPLA₂ activity in the murine intestinal tract utilizing a fluorescent BODIPY-labeled phospholipid substrate. Here, we report assay conditions that distinguish between secreted and cytosolic PLA₂ enzyme activities in extracts of intestinal tissue. The small intestine exhibited higher activity levels than the large intestine. Consistent with predictions from the sPLA₂-IIA gene sequence in inbred strains, we detected low levels of enzyme activity in inbred strains containing sPLA₂-IIA mutations; these strains were also associated with greater numbers of intestinal polyps. Additionally, the assay was able to distinguish differences in levels of sPLA₂ activity between neoplasia-resistant strains, which were then shown by sequencing to carry variant wild-type sPLA₂-IIA alleles. Immunohistochemical analyses of intestinal tissues were consistent with sPLA₂-IIA activity levels. This approach enables further studies of the mechanisms of sPLA₂ action influencing the development and tumorigenesis of the small intestine and colon in both mice and humans.

Comments

Diversity in secreted PLA2-IIA activity among inbred mouse strains that are resistant or susceptible to ApcMin/+ tumorigenesis (2005). Marina Markova, Revati A. Koratkar, Karen A. Silverman, Vincent E. Sollars, Melina MacPhee-Pellini, Rhonda Walters, Juan P. Palazzo, Arthur M. Buchberg, Linda D. Siracusa and Steven A. Farber. Oncogene 24, 6450-6458.

Open Web access provided by the publisher. All Rights Reserved. doi:10.1038/sj.onc.1208791

Recommended Citation

Diversity in secreted PLA2-IIA activity among inbred mouse strains that are resistant or susceptible to ApcMin/+ tumorigenesis (2005). Marina Markova, Revati A. Koratkar, Karen A. Silverman, Vincent E. Sollars, Melina MacPhee-Pellini, Rhonda Walters, Juan P. Palazzo, Arthur M. Buchberg, Linda D. Siracusa and Steven A. Farber. Oncogene 24, 6450-6458.