title: Proteomic and SAGE profiling of murine melanoma progression indicates the reduction of proteins responsible for ROS degradation.
abstract: Using 2-DE of total cell protein extracts, we compared soluble proteins from murine melanoma lines Tm1 and Tm5 with proteins from the nontumoral cell melan-a from which they were derived. Seventy-one of the 452 spots (average) detected with CBB were differentially accumulated, i.e., increased or decreased twofold. Forty-four spots were identified by PMF/MALDI-TOF, 15 with increased and 29 with decreased protein levels. SAGE showed that 17/34 (50%) of the differentially accumulated proteins, pI range 4-7, presented similar differences at the mRNA level. Major reductions in protein were observed in tumor cells of proteins that degrade reactive oxygen species (ROS). Decreases of > or = twofold in GST, superoxide dismutase, aldehyde dehydrogenase, thioredoxin, peroxiredoxin 2, and peroxiredoxin 6 protein were observed. SAGE indicated the reduction of other proteins involved in ROS degradation. As expected, the accumulation of exogenous peroxides was significantly higher in the tumor cells while the levels of glutathionylation were two times lower in the tumor cells compared to melan-a. The differential accumulation of proteins involved in oncogene/tumor suppressor pathways was observed. Melanoma cells can favor survival pathways activated by ROS by inhibiting p53 pathways and activation of Ras and c-myc pathways.
authors.affiliation: Centro de Terapia Celular, Centro Regional de Hemoterapia de Ribeirão Preto, Centro de Pesquisa, Inovação e Difusão - FAPESP, Brasil.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: de Souza
authors.forename: Lyris M F
authors.initials: LM
authors.lastname: Godoy
authors.forename: Veronica R
authors.initials: VR
authors.lastname: Teixeira
authors.forename: Andreia H
authors.initials: AH
authors.lastname: Otake
authors.forename: Adão
authors.initials: A
authors.lastname: Sabino
authors.forename: José C
authors.initials: JC
authors.lastname: Rosa
authors.forename: Anemari R
authors.initials: AR
authors.lastname: Dinarte
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Pinheiro
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Silva
authors.forename: Marcos N
authors.initials: MN
authors.lastname: Eberlin
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Greene
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; D016877:Oxidants; D020543:Proteome; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione