Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 47, Pages 19866-19871Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911545106
Keywords
immortalization; mitochondrial ribosomal protein
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Funding
- Swedish Cancer Society
- Concern Foundation (Los Angeles)
- Cancer Research Institute (New York)
- Swedish Institute
- Swedish Foundation for Strategic Research
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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 cell markers, such as SSEA-1, Sox2, and Oct3/4. In confluent cultures, a portion of cells also express ectodermand endoderm-specific pan-keratin, ectoderm-specific beta-III-tubulin, mesoderm-specific MHC class II, and become stainable for fat with Oil red O. None of these changes was detected in c-myc+Ha-ras (MR)-transformed cells. In immunodeficient mice, 18IM cells formed small transiently growing tumors that have down-regulated SSEA-1 and showed pan-keratin staining. We conclude that S18-2 can immortalize REFs and induces them to express stem cell traits.
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