Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle

Journal of Cellular and Molecular Medicine

Gabriella Czifra²  Attila Szöllősi²  Zsuzsanna Nagy²  Miklós Boros²  István Juhász¹  Andrea Kiss³  Ferenc Erdᔝi³  Tamás Szabó⁵  Ilona Kovács⁴  Miklós Török⁴  László Kovács²  Peter M. Blumberg⁶ 

[1] Department of Dermatology, Medical Faculty, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary;DE-MTA “Lendület” Cellular Physiology Research Group, Department of Physiology, Medical Faculty, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary;Department of Medical Chemistry, Medical Faculty, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary;Department of Pathology, Gyula Kenézy Hospital, Debrecen, Hungary;Department of Pediatrics, Medical Faculty, University of Debrecen, Research Center for Molecular Medicine, Debrecen, Hungary;Laboratory of Cancer Biology and Genetics Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

关键词: Skeletal muscle;    C2C12 myoblasts;    rhabdomyosarcoma;    protein kinase C;    nPKCδ;    PKC isoenzymes;    recombinant overexpression;    proliferation;    differentiation;    tumourigenesis;   

DOI  :  10.1111/jcmm.12452

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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