title: Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts.
abstract: We have shown earlier that overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts. The derived cells expressed the embryonic stem cell markers, and cellular pathways that control cell proliferation, oxidative phosphorylation, cellular respiration, and other redox reactions were activated in the immortalized cells.Here we report that, upon overexpression of S18-2 protein, primary rat skin fibroblasts underwent cell transformation. Cells passed more than 300 population doublings, and two out of three tested clones gave rise to tumors in experimental animals. Transformed cells showed anchorage-independent growth and loss of contact inhibition; they expressed epithelial markers, such as E-cadherin and β-catenin. Transformed cells showed increased telomerase activity, disturbance of the cell cycle, and chromosomal instability. Taken together, our data suggest that S18-2 is a newly identified oncoprotein that may be involved in cancerogenesis.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Suhas D
authors.initials: SD
authors.lastname: Darekar
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mushtaq
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sreeharsha
authors.initials: S
authors.lastname: Gurrapu
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine.
authors.forename: Larysa
authors.initials: L
authors.lastname: Kovalevska
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Catherine
authors.initials: C
authors.lastname: Drummond
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Petruchek
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.|King Abdullah University of Science and Technology, PSE and BESE Divisions, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Luca
authors.initials: L
authors.lastname: Tirinato
authors.affiliation: King Abdullah University of Science and Technology, PSE and BESE Divisions, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Enzo
authors.initials: E
authors.lastname: Di Fabrizio
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.|University "Magna Græcia" of Catanzaro, Viale Europa, Località Germaneto, Catanzaro, Italy.
authors.forename: Ennio
authors.initials: E
authors.lastname: Carbone
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.|R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine.
authors.forename: Elena
authors.initials: E
authors.lastname: Kashuba
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D043171:Chromosomal Instability; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007621:Karyotyping; D008055:Lipids / Q000737:chemistry; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D051381:Rats; D012269:Ribosomal Proteins / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism
chemical_list: D008055:Lipids; D012269:Ribosomal Proteins; C041184:ribosomal protein S18; D049452:Green Fluorescent Proteins; D019098:Telomerase; D010100:Oxygen
keywords: MRPS18-2; cell transformation; chromosomal instability; mitochondrial ribosomal protein; rat skin fibroblasts