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

G. Czifra, Attila Szöllosi, Zsuzsanna Nagy, Miklós Boros, I. Juhász, A. Kiss, F. Erdődi, Tamás Szabó, I. Kovács, Miklós Török, László Kovács, Peter M. Blumberg, T. Bíró

Research output: Article

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)396-407
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume19
Issue number2
DOIs
Publication statusPublished - febr. 1 2015

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Protein Kinase C
Skeletal Muscle
Growth
Protein Isoforms
Rhabdomyosarcoma
Neoplasms
SCID Mice
Myoblasts
Heterografts
Muscle Cells
Phosphotransferases
Cell Proliferation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle. / Czifra, G.; Szöllosi, Attila; Nagy, Zsuzsanna; Boros, Miklós; Juhász, I.; Kiss, A.; Erdődi, F.; Szabó, Tamás; Kovács, I.; Török, Miklós; Kovács, László; Blumberg, Peter M.; Bíró, T.

In: Journal of Cellular and Molecular Medicine, Vol. 19, No. 2, 01.02.2015, p. 396-407.

Research output: Article

Czifra, G. ; Szöllosi, Attila ; Nagy, Zsuzsanna ; Boros, Miklós ; Juhász, I. ; Kiss, A. ; Erdődi, F. ; Szabó, Tamás ; Kovács, I. ; Török, Miklós ; Kovács, László ; Blumberg, Peter M. ; Bíró, T. / Protein kinase Cδ promotes proliferation and induces malignant transformation in skeletal muscle. In: Journal of Cellular and Molecular Medicine. 2015 ; Vol. 19, No. 2. pp. 396-407.
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AU - Czifra, G.

AU - Szöllosi, Attila

AU - Nagy, Zsuzsanna

AU - Boros, Miklós

AU - Juhász, I.

AU - Kiss, A.

AU - Erdődi, F.

AU - Szabó, Tamás

AU - Kovács, I.

AU - Török, Miklós

AU - Kovács, László

AU - Blumberg, Peter M.

AU - Bíró, T.

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N2 - 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.

AB - 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.

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