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Diversity in secreted PLA2-IIA activity among inbred mouse strains that are resistant or susceptible to ApcMin/+ tumorigenesis

Oncogene volume 24, pages 6450–6458 (2005)Cite this article

Abstract

The secreted phospholipase A2 type IIA (Pla2g2a) gene was previously identified as a modifier of intestinal adenoma multiplicity in ApcMin/+ 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.

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Acknowledgements

We thank Dr EA Dennis for critical suggestions regarding this research, Dr R Mulherkar for graciously providing the sPLA2-IIA antibody and Dr H Alder for sequencing with the KCC Nucleic Acids Facility. This work was supported in part by US NIH Grants RO1 DK060369 (SAF), PO1CA72027 (LDS and AMB) and RO1 CA89560 (LDS and AMB) and by a Pew's Scholar's Award to SAF.

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Author notes

  1. Vincent E Sollars

    Present address: Joan C. Edwards, Department of Micro/Immuno/Mol Gen, School of Medicine, Marshall University, Huntington, WV, 25704-9388, USA

  2. Linda D Siracusa and Steven A Farber: Cosenior authors

Authors and Affiliations

  1. Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, 19107, PA, USA

    Marina Markova, Revati A Koratkar, Karen A Silverman, Vincent E Sollars, Melina MacPhee-Pellini, Arthur M Buchberg, Linda D Siracusa & Steven A Farber

  2. Department of Surgical Pathology, Thomas Jefferson University, Philadelphia, 19107, PA, USA

    Rhonda Walters & Juan P Palazzo

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  1. Marina Markova
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Correspondence to Steven A Farber.

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Markova, M., Koratkar, R., Silverman, K. et al. Diversity in secreted PLA2-IIA activity among inbred mouse strains that are resistant or susceptible to ApcMin/+ tumorigenesis. Oncogene 24, 6450–6458 (2005). https://doi.org/10.1038/sj.onc.1208791

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