title: c-Myc modulation: a key role in melanoma drug response.
abstract: Understanding molecular mechanisms involved in melanoma resistance to drugs is a big challenge. Experimental evidences suggested a correlation between mutational status in B-RAF and melanoma cell susceptibility to drugs, such as paclitaxel, doxorubicin and temozolomide, which generate an accumulation of hydrogen peroxide (H2O2) in the cells. We investigated the survival phenotype and the protein level of c-myc, a B-RAF target molecule, in melanoma cells, carrying a different mutational status in B-RAF, upon paclitaxel, doxorubicin and H2O2 treatment. For the first time, we reported c-myc modulation is critical for melanoma drug response. It appeared drug-specific and post-transcriptionally driven through PP2A; in correlation, cell pre-treatment with okadaic acid (OA), a specific PP2A inhibitor, as well as PP2A silencing of melanoma cells, was able to increase melanoma cell drug-sensitivity and c-myc protein level. This is relevant for designing efficacious therapeutic strategies in melanoma.
authors.affiliation: a Institute of Genetics and Biophysics; A Buzzati-Traverso ; Naples , Italy.|d These authors equally contributed to this work.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fico
authors.affiliation: a Institute of Genetics and Biophysics; A Buzzati-Traverso ; Naples , Italy.|d These authors equally contributed to this work.
authors.forename: Daniela
authors.initials: D
authors.lastname: Alfano
authors.affiliation: a Institute of Genetics and Biophysics; A Buzzati-Traverso ; Naples , Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Valentino
authors.affiliation: b Università degli Studi di Catania; Dipartimento di Scienze Bio-Mediche ; Catania , Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Vasta
authors.affiliation: c Istituto Nazionale Tumori Fondazione G Pascale ; Naples , Italy.
authors.forename: Ernesta
authors.initials: E
authors.lastname: Cavalcanti
authors.affiliation: b Università degli Studi di Catania; Dipartimento di Scienze Bio-Mediche ; Catania , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Travali
authors.affiliation: a Institute of Genetics and Biophysics; A Buzzati-Traverso ; Naples , Italy.
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Patriarca
authors.affiliation: a Institute of Genetics and Biophysics; A Buzzati-Traverso ; Naples , Italy.|b Università degli Studi di Catania; Dipartimento di Scienze Bio-Mediche ; Catania , Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Caputo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D003606:Dacarbazine; D004317:Doxorubicin; D006861:Hydrogen Peroxide; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2; D017239:Paclitaxel; D000077204:Temozolomide
keywords: B-RAF mutations; c-myc modulation; cancer therapy; chemotherapy; melanoma drug resistance, PP2A activity
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