Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation

Abstract

BACKGROUND: Growth factor, cytokine and chemokine-induced activationof PI3K enzymes constitutes the start of a complex signalling cascade,which ultimately mediates cellular activities such as proliferation,differentiation, chemotaxis, survival, trafficking, and glucose homeostasis.The PI3K enzyme family is divided into 3 classes; class I (subdividedinto IA and IB), class II (PI3K-C2alpha, PI3K-C2beta and PI3K-C2gamma)and class III PI3K. Expression of these enzymes in human tissue hasnot been clearly defined. METHODS: In this study, we analysed theimmunohistochemical topographical expression profile of class IA(anti-p85 adaptor) and class II PI3K (PI3K-C2alpha and PI3K-C2beta)enzymes in 104 formalin-fixed, paraffin embedded normal adult human(age 33-71 years, median 44 years) tissue specimens including thosefrom the gastrointestinal, genitourinary, hepatobiliary, endocrine,integument and lymphoid systems. Antibody specificity was verifiedby Western blotting of cell lysates and peptide blocking studies.Immunohistochemistry intensity was scored from undetectable to strong.RESULTS: PI3K enzymes were expressed in selected cell populationsof epithelial or mesenchymal origin. Columnar epithelium and transitionalepithelia were reactive but mucous secreting and stratified squamousepithelia were not. Mesenchymal elements (smooth muscle and endothelialcells) and glomerular epithelium were only expressed PI3K-C2alphawhile ganglion cells expressed p85 and PI3K-C2beta. All three enzymeswere detected in macrophages, which served as an internal positivecontrol. None of the three PI3K isozymes was detected in the stemcell/progenitor compartments or in B lymphocyte aggregates. CONCLUSIONS:Taken together, these data suggest that PI3K enzyme distributionis not ubiquitous but expressed selectively in fully differentiated,non-proliferating cells. Identification of the normal in vivo expressionpattern of class IA and class II PI3K paves the way for further analyseswhich will clarify the role played by these enzymes in inflammatory,neoplastic and other human disease conditions.