title: Protein kinase Cδ in tumorigenesis of human malignant fibrous histiocytoma.
abstract: Protein kinase Cδ (PKCδ), an isoform of PKC, has been shown to act as a critical mediator of tumor progression and apoptosis; however, its role in musculoskeletal tumors is still unknown. In the current study, we examined the expression of PKCδ in human musculoskeletal tumor tissue samples, and investigated the effects of siRNA downregulation of PKCδ on human malignant fibrous histiocytoma (MFH) cell proliferation, migration, and apoptosis, to elucidate its functional roles in musculoskeletal tumorigenesis. Of note, real-time PCR analysis revealed that mRNA expression of PKCδ in high-grade musculoskeletal MFH tumors was significantly lower than that in benign schwannomas. siRNA downregulation of PKCδ significantly increased human MFH cell proliferation and migration, and markedly suppressed apoptosis. These findings suggest that PKCδ has a negative effect on tumorigenesis and/or acts as a pro-apoptotic kinase in human MFH cells. The data presented here could be applied in the development of new therapeutic avenues, with the elevation of PKCδ expression being one potential strategy to prevent MFH progression. Thus, PKCδ may be a potent therapeutic target for human MFH.
authors.affiliation: Department of Orthopedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Naomasa
authors.initials: N
authors.lastname: Fukase
authors.forename: Teruya
authors.initials: T
authors.lastname: Kawamoto
authors.forename: Kenta
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Hitomi
authors.initials: H
authors.lastname: Hara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Okada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Onishi
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Toda
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Akisue
mesh_terms: D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D051677:Histiocytoma, Malignant Fibrous / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D051745:Protein Kinase C-delta / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051745:Protein Kinase C-delta