title: Ectopic overexpression of Nanog induces tumorigenesis in non-tumorous fibroblasts.
abstract: Key regulatory genes in pluripotent stem cells are of interest not only as reprogramming factors but also as regulators driving tumorigenesis. Nanog is a transcription factor involved in the maintenance of embryonic stem cells and is one of the reprogramming factors along with Oct4, Sox2, and Lin28. Nanog expression has been detected in different types of tumors, and its expression is a poor prognosis for cancer patients. However, there is no clear evidence that Nanog is functionally involved in tumorigenesis. In this study, we induced overexpression of Nanog in mouse embryonic fibroblast cells and subsequently assessed their morphological changes, proliferation rate, and tumor formation ability. We found that Nanog overexpression induced immortalization of mouse embryonic fibroblast cells (MEFs) and increased their proliferation rate in vitro. We also found that formation of tumors after subcutaneous injection of retroviral-Nanog infected MEFs (N-MEFs) into athymic mouse. Cancer-related genes such as Bmi1 were expressed at high levels in N-MEFs. Hence, our results demonstrate that Nanog is able to transform normal somatic cells into tumor cells.
authors.forename: Yo Seph
authors.initials: YS
authors.lastname: Park
authors.forename: Judee Grace E
authors.initials: JG
authors.lastname: Nemeño
authors.forename: Na Young
authors.initials: NY
authors.lastname: Choi
authors.forename: Jeong Ik
authors.initials: JI
authors.lastname: Lee
authors.forename: Kisung
authors.initials: K
authors.lastname: Ko
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Choi
authors.forename: Wan Seop
authors.initials: WS
authors.lastname: Kim
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Han
authors.forename: Natalia
authors.initials: N
authors.lastname: Tapia
authors.forename: Kinarm
authors.initials: K
authors.lastname: Ko
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D000071317:Nanog Homeobox Protein; D015854:Up-Regulation
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse