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

Research output: Contribution to journalArticlepeer-review

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 ß-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.

Original languageEnglish
Pages (from-to)21016-21028
Number of pages13
JournalOncotarget
Volume6
Issue number25
Publication statusPublished - 2015

Keywords

  • Cell transformation
  • Chromosomal instability
  • Mitochondrial ribosomal protein
  • MRPS18-2
  • Rat skin fibroblasts

ASJC Scopus subject areas

  • Oncology

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