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 cell markers, such as SSEA-1, Sox2, and Oct3/4. In confluent cultures, a portion of cells also express ectoderm- and 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.
Kashuba
Elena
E
Department of Microbiology, Karolinska Institutet, BOX 280, S-17177 Stockholm, Sweden.
Pavan Yenamandra
Surya
S
Darekar
Suhas Deoram
SD
Yurchenko
Mariya
M
Kashuba
Vladimir
V
Klein
George
G
Szekely
Laszlo
L
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D017690:Cell Transplantation; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D011993:Recombinant Fusion Proteins; D012269:Ribosomal Proteins; C041184:ribosomal protein S18