Protein kinase C expression links natural antibody binding with surveillance of activated and preneoplastic cells.
Extensive evidence supports a role for natural antibody (NAb) acting against small tumour foci in vivo. Ras-transformation of murine C3H 10T 1/2 fibroblasts, known to partially activate and down-regulate endogenous PKC-alpha, increased their serum NAb-binding capacity consistent with the requirements for natural immune surveillance. Now a rat PKC-beta1-overexpressing 10T 1/2 clone, PKC-4, with an 11-fold increase in PKC activity and an activated, partially transformed phenotype, links higher susceptibility to transformation through v-Ha-ras infection with an 80% increase in NAb binding assayed by flow cytometry. H7 and E-64d inhibition and phorbol ester depletion of PKC reduced NAb binding. PKC-beta1 expression and NAb binding exhibited a similar temporal recovery from TPA treatment. Thus, expression of NAb-binding structures appears to be elevated by constitutive increases in the basal activation of PKC in both the ras-transformation and the PKC-beta1-preneoplasia models. This, coupled with corresponding decreases in membrane PKC-alpha and NAb binding in confluent 10T 1/2 cells raises the possibility that in general, cells activated through PKC are NAb sensitive. Together with the increased in vivo elimination of the high NAb-binding PKC-4 cells, the data extend the support for a role for NAb in immune surveillance, to resistance against preneoplastic cells, and argue for NAb contributing to homeostasis of the organism.
Wang
H
H
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Chow
D A
DA
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000818:Animals; D001666:Binding Sites, Antibody / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D011905:Genes, ras / Q000276:immunology; D007113:Immunity, Innate; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011230:Precancerous Conditions / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D064546:Protein Kinase C beta; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D013755:Tetradecanoylphorbol Acetate