title: Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle.
abstract: In this paper, we investigated the isoform-specific roles of certain protein kinase C (PKC) isoforms in the regulation of skeletal muscle growth. Here, we provide the first intriguing functional evidence that nPKCδ (originally described as an inhibitor of proliferation in various cells types) is a key player in promoting both in vitro and in vivo skeletal muscle growth. Recombinant overexpression of a constitutively active nPKCδ in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase-negative mutant of nPKCδ (DN-nPKCδ) markedly inhibited cell growth. Moreover, overexpression of nPKCδ also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient (SCID) mice whereas that of DN-nPKCδ suppressed tumour formation. The role of nPKCδ in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKCδ in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated (PKCα, β, ε) exerted only minor (mostly growth-inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKCδ as a novel growth-promoting molecule in skeletal muscles and invite further trials to exploit its therapeutic potential in the treatment of skeletal muscle malignancies.
authors.affiliation: DE-MTA "Lendület" Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Czifra
authors.forename: Attila
authors.initials: A
authors.lastname: Szöllősi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Nagy
authors.forename: Miklós
authors.initials: M
authors.lastname: Boros
authors.forename: István
authors.initials: I
authors.lastname: Juhász
authors.forename: Andrea
authors.initials: A
authors.lastname: Kiss
authors.forename: Ferenc
authors.initials: F
authors.lastname: Erdődi
authors.forename: Tamás
authors.initials: T
authors.lastname: Szabó
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovács
authors.forename: Miklós
authors.initials: M
authors.lastname: Török
authors.forename: László
authors.initials: L
authors.lastname: Kovács
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
authors.forename: Tamás
authors.initials: T
authors.lastname: Bíró
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D051745:Protein Kinase C-delta / Q000378:metabolism*
chemical_list: D051745:Protein Kinase C-delta
keywords: C2C12 myoblasts; PKC isoenzymes; Skeletal muscle; differentiation; nPKCδ; proliferation; protein kinase C; recombinant overexpression; rhabdomyosarcoma; tumourigenesis