Association of elevated levels of protein kinase C‐ζ mrna and protein with murine B‐lymphocytic neoplasia

Abstract

Expression of mRNA for protein kinase C (PKC)-alpha, -beta, -gamma, -delta, -epsilon, -zeta, and -eta has been shown, by polymerase chain reaction-generated isozyme-specific probes, to be cell-type -and differentiation-stage-specific in mouse hemopoietic cells. Recently, we cloned a 2.2-kb mouse PKC -zeta cDNA. In this study, we used the nearly full-length cDNA PKC-zeta probe to demonstrate that expression of PKC-zeta was significantly elevated in lymphocytic neoplasms at both the mRNA and protein levels. Normal brain, kidney, and liver contain 2.4- and 4.4-kb mRNAs, whereas normal lymphoid organs (spleen, thymus, and lymph nodes) express barely detectable amounts of PKC-zeta. These vanishingly small levels of PKC-zeta mRNA did not increase when polyclonal spleen B-cell proliferation and differentiation were induced in vivo with anti-immunoglobulin D antiserum or in vitro with lipopolysaccharide. In contrast, 2.4-kb transcripts of PKC-zeta are abundant in virtually all neoplastic B-lymphocytic cell lines. Furthermore, additional transcripts of a novel size, about 7 and 8 kb, were found in several mature B-cell lymphomas and plasma cell tumors. Western blot analysis of protein extracts from normal B cells and hemopoietic tumors confirmed that these quantitative differences in PKC-zeta mRNA also exist at the protein level. That is, only trace amounts of PKC-zeta protein were detectable in pro-B cells and pre-B cells, but abundant amounts of this isoform were found in protein extracts from most B-cell lymphomas and plasma cell tumors. These findings suggest that this atypical member of the PKC multigene family participate in the multistep process of malignant transformation of lymphocytes.

Role of N-Cadherin and Protein Kinase C in Osteoblast Gene Activation Induced by the S252W Fibroblast Growth Factor Receptor 2 Mutation in Apert Craniosynostosis

“…This supports the hypothesis that PKCα may be implicated in the overexpression of N‐cadherin and osteoblast genes induced by the mutation in Ap cells. Although our data are consistent with a role of PKCα in the N‐cadherin and osteoblast gene overexpression induced by the activating S252W FGFR‐2 mutation, we cannot rule out that other PKC isoforms, not yet identified, also may be involved in the increased osteoblast phenotype in mutant cells, because several PKC isoforms may play critical roles in the control of cell differentiation in different cell systems (59) . Recent data indicate that PKC may play a key role in chondrogenic differentiation and that PKC signaling is coupled with the regulation of N‐cadherin during chondrogenesis (60) .…”

PKC ζ–mTOR pathway: a new target for rituximab therapy in follicular lymphoma

“…26 In mice, previous studies have shown that, whereas normal lymphoid organs (spleen, thymus, and lymph nodes) express barely detectable amounts of PKC, the expression of the enzyme increases in most murine B-cell lymphomas and plasma tumor cells tested. 27 This provocative result was not extended to human B cells until our study. The lack of information about PKC distribution in human tissue samples is likely because that there is no antibody from a commercial source available for immunohistochemistry.…”