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dc.contributor.authorMattaini, Katherine R.
dc.contributor.authorSullivan, Mark R.
dc.contributor.authorLau, Allison N.
dc.contributor.authorFiske, Brian P.
dc.contributor.authorVander Heiden, Matthew G.
dc.date.accessioned2020-04-08T14:35:03Z
dc.date.available2020-04-08T14:35:03Z
dc.date.issued2019-07-22
dc.identifier.issn1471-2407
dc.identifier.urihttps://hdl.handle.net/1721.1/124524
dc.description.abstractBackground: Copy number gain of the D-3-phosphoglycerate dehydrogenase (PHGDH) gene, which encodes the first enzyme in serine biosynthesis, is found in some human cancers including a subset of melanomas. Methods: In order to study the effect of increased PHGDH expression in tissues in vivo, we generated mice harboring a PHGDH tetO allele that allows tissue-specific, doxycycline-inducible PHGDH expression, and we analyzed the phenotype of mice with a ubiquitous increase in PHGDH expression. Results: Tissues and cells derived from PHGDH tetO mice exhibit increased serine biosynthesis. Histological examination of skin tissue from PHGDH tetO mice reveals the presence of melanin granules in early anagen hair follicles, despite the fact that melanin synthesis is closely coupled to the hair follicle cycle and does not normally begin until later in the cycle. This phenotype occurs in the absence of any global change in hair follicle cycle timing. The aberrant presence of melanin early in the hair follicle cycle following PHGDH expression is also accompanied by increased melanocyte abundance in early anagen skin. Conclusions: These data suggest increased PHGDH expression impacts normal melanocyte biology, but PHGDH expression alone is not sufficient to cause cancer.en_US
dc.description.sponsorshipKoch Institute for Integrative Cancer Research (Grant (P30-CA14051)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowship Program (DGE-1122374)en_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundation (Grant DRG-2241-15)en_US
dc.description.sponsorshipLudwig Center for Molecular Oncology at MIT (Grant 21-CA198028)en_US
dc.description.sponsorshipLudwig Center for Molecular Oncology at MIT (Grant R01-CA168653)en_US
dc.language.isoen
dc.publisherSpringer Science and Business Media LLCen_US
dc.relation.isversionof10.1186/s12885-019-5933-5en_US
dc.rightsCreative Commons Attribution 4.0 International licenseen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceBioMed Central (BMC)en_US
dc.subjectGeneticsen_US
dc.subjectCancer Researchen_US
dc.subjectOncologyen_US
dc.titleIncreased PHGDH expression promotes aberrant melanin accumulationen_US
dc.typeArticleen_US
dc.identifier.citationMattaini, Katherine R. et al. "Increased PHGDH expression promotes aberrant melanin accumulation." BMC cancer 19 (2019): :723 © 2019 The Author(s)en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.relation.journalBMC canceren_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2020-01-30T16:52:48Z
dspace.date.submission2020-01-30T16:52:50Z
mit.journal.volume19en_US
mit.journal.issue1en_US
mit.licensePUBLISHER_CC


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