Open AccessProtein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle
Author(s) -
Czifra Gabriella,
Szöllősi Attila,
Nagy Zsuzsanna,
Boros Miklós,
Juhász István,
Kiss Andrea,
Erdődi Ferenc,
Szabó Tamás,
Kovács Ilona,
Török Miklós,
Kovács László,
Blumberg Peter M.,
Bíró Tamás
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12452
Subject(s) - skeletal muscle , cell growth , c2c12 , myocyte , rhabdomyosarcoma , biology , microbiology and biotechnology , kinase , in vivo , gene isoform , cancer research , endocrinology , sarcoma , medicine , biochemistry , pathology , myogenesis , gene
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 nPKC δ (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 nPKC δ in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase‐negative mutant of nPKC δ ( DN ‐ nPKC δ) markedly inhibited cell growth. Moreover, overexpression of nPKC δ also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient ( SCID ) mice whereas that of DN ‐ nPKC δ suppressed tumour formation. The role of nPKC δ in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKC δ in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated ( PKC α, β, ε) exerted only minor (mostly growth‐inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKC δ 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.