|Human skin neural crest progenitor cells are susceptible to BRAF(V600E)-induced transformation.|
|PMID: 23334329 Owner: NLM Status: MEDLINE|
|Adult stem cells are multipotent and persist in small numbers in adult tissues throughout the lifespan of an organism. Unlike differentiated cells, adult stem cells are intrinsically resistant to senescence. It is unclear how adult stem cells in solid organs respond to oncogenic stimulation and whether these cells have a role in tumor initiation. We report here that expression of BRAF(V600E) in human neural crest progenitor cells (hNCPCs) did not induce growth arrest as seen in human melanocytes, but instead, increased their cell proliferation capacity. These cells (hNCPCs(V600E)) acquired anchorage-independent growth ability and were weakly tumorigenic in vivo. Unlike in human melanocytes, BRAF(V600E) expression in hNCPCs did not induce p16(INK4a) expression. BRAF(V600E) induced elevated expression of CDK2, CDK4, MITF and EST1/2 protein in hNCPCs, and also induced melanocytic differentiation of these cells. Furthermore, overexpression of MITF in hNCPCs(V600E) dramatically increased their tumorigenicity and resulted in fully transformed tumor cells. These findings indicate that hNCPCs are susceptible to BRAF(V600E)-induced transformation, and MITF potentiates the oncogenic effect of BRAF(V600E) in these progenitor cells. These results suggest that the hNCPCs are potential targets for BRAF(V600E)-induced melanocytic tumor formation.|
|S M Kumar; J Dai; S Li; R Yang; H Yu; K L Nathanson; S Liu; H Zhou; J Guo; X Xu|
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|Type: Journal Article; Research Support, N.I.H., Extramural Date: 2013-01-21|
|Title: Oncogene Volume: 33 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2014 Feb|
|Created Date: 2014-02-13 Completed Date: 2014-04-14 Revised Date: 2014-05-02|
Medline Journal Info:
|Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England|
|Languages: eng Pagination: 832-41 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Adult Stem Cells
Cell Transformation, Neoplastic / genetics*, metabolism, pathology
DNA Copy Number Variations
Melanoma / genetics, metabolism, pathology
Mice, Inbred NOD
Microphthalmia-Associated Transcription Factor / genetics
Neural Crest / pathology*
Neural Stem Cells / metabolism*, pathology
Proto-Oncogene Proteins B-raf / genetics*, metabolism
Skin / pathology*
|AR-054593/AR/NIAMS NIH HHS; CA-116103/CA/NCI NIH HHS; P01 CA025874/CA/NCI NIH HHS; P01 CA114046/CA/NCI NIH HHS; P30 CA016520/CA/NCI NIH HHS; R01 AR054593/AR/NIAMS NIH HHS; R21 CA116103/CA/NCI NIH HHS|
|0/MITF protein, human; 0/Microphthalmia-Associated Transcription Factor; EC 18.104.22.168/BRAF protein, human; EC 22.214.171.124/Proto-Oncogene Proteins B-raf|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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