Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

Suhas D. Darekar; Muhammad Mushtaq; Sreeharsha Gurrapu; Larysa Kovalevska; Catherine Drummond; Maria Petruchek; Luca Tirinato; Enzo Di Fabrizio; Ennio Carbone; Elena Kashuba

doi:10.18632/oncotarget.4123

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Research Papers:

Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

Suhas D. Darekar, Muhammad Mushtaq, Sreeharsha Gurrapu, Larysa Kovalevska, Catherine Drummond, Maria Petruchek, Luca Tirinato, Enzo Di Fabrizio, Ennio Carbone and Elena Kashuba _

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Oncotarget. 2015; 6:21016-21028. https://doi.org/10.18632/oncotarget.4123

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Abstract

Suhas D. Darekar1, Muhammad Mushtaq1, Sreeharsha Gurrapu1, Larysa Kovalevska2, Catherine Drummond1, Maria Petruchek1, Luca Tirinato1,3, Enzo Di Fabrizio3, Ennio Carbone1,4 and Elena Kashuba1,2

1 Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden

2 R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine

3 King Abdullah University of Science and Technology, PSE and BESE Divisions, Thuwal, Kingdom of Saudi Arabia

4 University “Magna Græcia” of Catanzaro, Viale Europa, Località Germaneto, Catanzaro, Italy

Correspondence to:

Elena Kashuba, email:

Keywords: MRPS18-2, cell transformation, mitochondrial ribosomal protein, rat skin fibroblasts, chromosomal instability

Received: April 04, 2015 Accepted: May 04, 2015 Published: May 12, 2015

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.

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Research Papers:

Mitochondrial ribosomal protein S18-2 evokes chromosomal instability and transforms primary rat skin fibroblasts

Abstract