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

نویسندگان

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

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Overexpression of MRPS18-2 in Cancer Cell Lines Results in Appearance of Multinucleated Cells

Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3. We discovered that overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts. Cells showed anchorage-independent growth pattern. Moreover, pathways characteristic for rapidly proliferating cells were upr...

متن کامل

Rat embryonic fibroblasts immortalized by MRPS18-2 protein are target for NK-cells

Overexpression of the human mitochondrial ribosomal protein MRPS18-2 (S18-2) led to immortalization of primary rat embryonic fibroblasts (REFs). The derived cells (18IM) expressed embryonic stem cell markers. Noteworthy, genes encoding the COX family proteins were up-regulated significantly. It is known that the COX family proteins are involved in the regulation of immune response. In the prese...

متن کامل

MRPS18-2 protein immortalizes primary rat embryonic fibroblasts and endows them with stem cell-like properties.

We report that the overexpression of mitochondrial ribosomal protein MRPS18-2 (S18-2) can immortalize primary rat embryonic fibroblasts (REFs). The immortalized cells (18IM) lose contact inhibition, form foci, and are capable of anchorage-independent growth. Concurrently, mesodermal markers, such as vimentin, smooth muscle actin, and Fut4, disappear completely. 18IM cells express embryonic stem...

متن کامل

Induction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields

Background: Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields (ELF-EMF) have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to ELF-EMF may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk es...

متن کامل

Reduced dosage of genes encoding ribosomal protein S18 suppresses a mitochondrial initiation codon mutation in Saccharomyces cerevisiae.

A yeast mitochondrial translation initiation codon mutation affecting the gene for cytochrome oxidase subunit III (COX3) was partially suppressed by a spontaneous nuclear mutation. The suppressor mutation also caused cold-sensitive fermentative growth on glucose medium. Suppression and cold sensitivity resulted from inactivation of the gene product of RPS18A, one of two unlinked genes that code...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015