Association of elevated levels of protein kinase C-zeta mRNA and protein with murine B-lymphocytic neoplasia.
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.