Please use this identifier to cite or link to this item: https://doi.org/10.1038/onc.2012.614
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dc.titleInduction of cells with cancer stem cell properties from nontumorigenic human mammary epithelial cells by defined reprogramming factors
dc.contributor.authorNishi, M.
dc.contributor.authorSakai, Y.
dc.contributor.authorAkutsu, H.
dc.contributor.authorNagashima, Y.
dc.contributor.authorQuinn, G.
dc.contributor.authorMasui, S.
dc.contributor.authorKimura, H.
dc.contributor.authorPerrem, K.
dc.contributor.authorUmezawa, A.
dc.contributor.authorYamamoto, N.
dc.contributor.authorLee, S.W.
dc.contributor.authorRyo, A.
dc.date.accessioned2016-09-06T08:19:09Z
dc.date.available2016-09-06T08:19:09Z
dc.date.issued2014-01-30
dc.identifier.citationNishi, M., Sakai, Y., Akutsu, H., Nagashima, Y., Quinn, G., Masui, S., Kimura, H., Perrem, K., Umezawa, A., Yamamoto, N., Lee, S.W., Ryo, A. (2014-01-30). Induction of cells with cancer stem cell properties from nontumorigenic human mammary epithelial cells by defined reprogramming factors. Oncogene 33 (5) : 643-652. ScholarBank@NUS Repository. https://doi.org/10.1038/onc.2012.614
dc.identifier.issn09509232
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/126730
dc.description.abstractCancer stem cells (CSCs), a small and elusive population of undifferentiated cancer cells within tumors that drive tumor growth and recurrence, are believed to resemble normal stem cells. Although surrogate markers have been identified and compelling CSC theoretical models abound, actual proof for the existence of CSCs can only be had retrospectively. Hence, great store has come to be placed in isolating CSCs from cancers for in-depth analysis. On the other hand, although induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, concern exists over the inadvertent co-transplantation of partially or undifferentiated stem cells with tumorigenic capacity. Here we demonstrate that the introduction of defined reprogramming factors (OCT4, SOX2, Klf4 and c-Myc) into MCF-10A nontumorigenic mammary epithelial cells, followed by partial differentiation, transforms the bulk of cells into tumorigenic CD44 + /CD24 low cells with CSC properties, termed here as induced CSC-like-10A or iCSCL-10A cells. These reprogrammed cells display a malignant phenotype in culture and form tumors of multiple lineages when injected into immunocompromised mice. Compared with other transformed cell lines, cultured iCSCL-10A cells exhibit increased resistance to the chemotherapeutic compounds, Taxol and Actinomycin D, but higher susceptibility to the CSC-selective agent Salinomycin and the Pin1 inhibitor Juglone. Restored expression of the cyclin-dependent kinase inhibitor p16INK4a abrogated the CSC properties of iCSCL-10A cells, by inducing cellular senescence. This study provides some insight into the potential oncogenicity that may arise via cellular reprogramming, and could represent a valuable in vitro model for studying the phenotypic traits of CSCs per se. © 2014 Macmillan Publishers Limited All rights reserved.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1038/onc.2012.614
dc.sourceScopus
dc.subjectCancer stem cell
dc.subjectMCF-10A
dc.subjectoncogenesis
dc.subjectp16INK4a
dc.subjectreprogramming factors
dc.typeArticle
dc.contributor.departmentMICROBIOLOGY
dc.description.doi10.1038/onc.2012.614
dc.description.sourcetitleOncogene
dc.description.volume33
dc.description.issue5
dc.description.page643-652
dc.description.codenONCNE
dc.identifier.isiut000331125100012
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