title: Overexpressed PKCδ downregulates the expression of PKCα in B16F10 melanoma: induction of apoptosis by PKCδ via ceramide generation.
abstract: In the present study, we observed a marked variation in the expression of PKCα and PKCδ isotypes in B16F10 melanoma tumor cells compared to the normal melanocytes. Interestingly, the tumor instructed expression or genetically manipulated overexpression of PKCα isotype resulted in enhanced G1 to S transition. This in turn promoted cellular proliferation by activating PLD1 expression and subsequent AKT phosphorylation, which eventually resulted in suppressed ceramide generation and apoptosis. On the other hand, B16F10 melanoma tumors preferentially blocked the expression of PKCδ isotype, which otherwise could exhibit antagonistic effects on PKCα-PLD1-AKT signaling and rendered B16F10 cells more sensitive to apoptosis via generating ceramide and subsequently triggering caspase pathway. Hence our data suggested a reciprocal PKC signaling operational in B16F10 melanoma cells, which regulates ceramide generation and provide important clues to target melanoma cancer by manipulating the PKCδ-ceramide axis.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Kuntal
authors.initials: K
authors.lastname: Halder
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Sayantan
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Anamika
authors.initials: A
authors.lastname: Bose
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D002518:Ceramides / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D007527:Isoenzymes; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D010739:Phospholipase D / Q000378:metabolism; D011485:Protein Binding; D051571:Protein Kinase C-alpha / Q000235:genetics*; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002518:Ceramides; D007527:Isoenzymes; D051057:Proto-Oncogene Proteins c-akt; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D010739:Phospholipase D; C106801:phospholipase D1