title: Protein kinase C: a putative new target for the control of human medullary thyroid carcinoma cell proliferation in vitro.
abstract: We investigate the role of protein kinase C (PKC) in the control of medullary thyroid carcinoma (MTC) cell proliferation by a PKC inhibitor, Enzastaurin, in human MTC primary cultures and in the TT cell line. We found that PKC inhibition reduces cell proliferation by inducing caspase-mediated apoptosis and blocks the stimulatory effect of IGF-I on calcitonin secretion. Enzastaurin reduces PKCβII (Thr500) phosphorylation, indicating a direct involvement of this isoform as well as the phosphorylated levels of Akt (Ser 473) and glycogen synthase kinase (Ser9), PKC pathway downstream targets and pharmacodynamic markers for PKC inhibition. PKCβII and PKCδ enzyme isoforms expression and localization were investigated. These data indicate that in vitro PKC is involved in the control of human MTC proliferation and survival by modulating apoptosis, with a mechanism that implicates PKCβII inhibition and translocation in different subcellular compartments. Targeting PKC may represent a useful therapeutic approach for controlling MTC proliferation.
authors.affiliation: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44121 Ferrara, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Molè
authors.forename: Erica
authors.initials: E
authors.lastname: Gentilin
authors.forename: Teresa
authors.initials: T
authors.lastname: Gagliano
authors.forename: Federico
authors.initials: F
authors.lastname: Tagliati
authors.forename: Marta
authors.initials: M
authors.lastname: Bondanelli
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Pelizzo
authors.forename: Martina
authors.initials: M
authors.lastname: Rossi
authors.forename: Carlo
authors.initials: C
authors.lastname: Filieri
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pansini
authors.forename: Ettore C
authors.initials: EC
authors.lastname: degli Uberti
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D018276:Carcinoma, Medullary / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; C504878:enzastaurin