Increased PHGDH expression promotes aberrant melanin accumulation
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document.pdf
Description
Published version
Size
1.15 MB
Format
Adobe PDF
Checksum (MD5)
15373998a7eaeca21128194b2668910e
Author(s)
Mattaini, Katherine R.
Sullivan, Mark R.
Lau, Allison N.
Fiske, Brian P.
Vander Heiden, Matthew G.
Date Issued
July 22, 2019
Journal
BMC cancer
Publisher
Springer Science and Business Media LLC
Citation
Mattaini, Katherine R. et al. "Increased PHGDH expression promotes aberrant melanin accumulation." BMC cancer 19 (2019): :723 © 2019 The Author(s)
Version
Final published version
Abstract
Background: 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.
Subjects
Genetics
Cancer Research
Oncology
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/s12885-019-5933-5
