The roles of sPLA2-IIA (Pla2g2a) in cancer of the small and large intestine.
The mouse secretory phospholipase A2 group IIA (sPLA2-IIA) gene Pla2g2a has been identified as a susceptibility gene for cancer of the small and large intestine. Interestingly, unlike most previously identified tumor susceptibility genes, Pla2g2a does not behave like a classical oncogene or tumor suppressor gene. Hence, identification of its biological functions in tumor development may shed new light on general mechanisms that modulate colon cancer risk. So far, sPLA2-IIA has been proposed to play a role in anti-bacterial defense, inflammation and eicosanoid generation, in clearance of apoptotic cells, and in the Wnt signaling pathway. More recently, comparison of RNA expression profiles of colon from Pla2g2a-transgenic to Pla2g2a-deficient mice confirmed and even extended sPLA2-IIA's diverse biological effects. In this review we aim to summarize current knowledge about the various links of sPLA2-IIA to cancer of the gastro-intestinal tract, and propose several models to illustrate its putative biological effects on tumor development.
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Remond J A
RJ
Fijneman
Robert T
RT
Cormier
D000818:Animals; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D054501:Group II Phospholipases A2 / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D007414:Intestinal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D051880:Receptors, Notch / Q000502:physiology; D015398:Signal Transduction; D051153:Wnt Proteins / Q000502:physiology
D051880:Receptors, Notch; D051153:Wnt Proteins; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human; C516288:Pla2g2a protein, mouse