title: C-MYC modulation induces responsiveness to paclitaxel in adrenocortical cancer cell lines.
abstract: C-MYC is overexpressed in many types of cancer linked to poor prognosis. We examined the c-Myc protein expression in adrenocortical cancer (ACC) cells to investigate the role of this protein in the neoplasm, its involvement in chemotherapy and finally to determine whether c-Myc could be considered a prognostic factor in patients with ACC. H295R and SW13 cell lines were treated with paclitaxel. c-Myc overexpressing cell clones were achieved by transfecting the H295R cell line with the pcDNA3-hMYC plasmid expressing the full-lengh C-MYC coding sequence. The SW13 cell line was transfected with siRNA oligonucleotides for C-MYC. Cell cycle analysis was evaluated by flow cytometry. c-Myc, cyclin B1 and pro caspase expression levels were evaluated by western blot analysis. We found that expression of c-Myc was highly expressed in the SW13 cells, whereas the protein was undetectable in the H295R cells. Different doses of paclitaxel were required in the two ACC cell line to induce a block in the G2 phase, characterized by increased cyclin B1 levels and to induce apoptosis by pro-caspase-3 activation. Interestingly, the silencing of C-MYC mRNA prevented paclitaxel induced apoptosis in SW13 cells, whereas in the H295R cells the overexpression of C-MYC rendered the cells more prone to growth inhibition after paclitaxel exposure. The present study directly demonstrates that C-MYC plays a central role in controlling proliferation in ACC cells after paclitaxel treatment and that c-Myc could be considered as a marker for predicting response to chemotherapeutic agents in ACC cell lines.
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Cerquetti
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Sampaoli
authors.affiliation: Research Center 'Bambino Gesù', Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: De Salvo
authors.affiliation: Research Center, San Pietro Hospital, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bucci
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Argese
authors.affiliation: Department of Pharmacy, University of Calabria, Cosenza, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Chimento
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Vottari
authors.affiliation: Research Center, San Pietro Hospital, Rome, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Marchese
authors.affiliation: Department of Pharmacy, University of Calabria, Cosenza, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pezzi
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Toscano
authors.affiliation: Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, 'Sapienza' University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Stigliano
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D017239:Paclitaxel / Q000494:pharmacology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D017239:Paclitaxel