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Association of elevated levels of protein kinase C‐ζ mrna and protein with murine B‐lymphocytic neoplasia
Author(s) -
Goodnight Joanne,
Mischak Harald,
Mushinski J. Frederic
Publication year - 1994
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940110303
Subject(s) - biology , microbiology and biotechnology , protein kinase c , b cell , messenger rna , complementary dna , kinase , antibody , biochemistry , immunology , gene
Expression of mRNA for protein kinase C(PKC)‐α, ‐β, ‐γ, ‐δ, ‐ϵ, ‐ζ, and ‐η 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 ‐ζ cDNA. In this study, we used the nearly full‐length cDNA PKC ‐ζ probe to demonstrate that expression of PKC‐ζ 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 ‐ζ. These vanishingly small levels of PKC ‐ζ 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‐ζ 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 ‐ζ mRNA also exist at the protein level. That is, only trace amounts of PKC‐ζ 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 participates in the multistep process of malignant transformation of lymphocytes.