Ectopic expression of c-Myc in the skin affects the hair growth cycle and causes an enlargement of the sebaceous gland
Abstract
Background The hair follicle continually undergoes dynamic remodelling in a cyclical manner involving tightly coordinated patterns of cell proliferation, differentiation and apoptosis. The oncoprotein c-Myc is a key regulator of these events in epidermal keratinocytes, but its importance in the hair growth cycle has not previously been determined. Objectives To determine the role of c-Myc in the hair growth cycle. Methods We characterized the hair follicle phenotype of transgenic mice that permit expression of a switchable form of c-Myc (c-Myc-ER) in the suprabasal epithelial layers of the epidermis and hair follicle. Results c-Myc activation increased epithelial cell proliferation in the outer root sheath and distal hair follicle, without any substantial alteration in levels of apoptosis. Moreover, chronic c-Myc activation resulted in marked desynchronization of the murine hair growth cycle, uncoupling of hair cycle-related skin thickness and enlargement of the sebaceous gland. Conclusions These data implicate c-Myc in the control of hair growth cycling and hair cycle-related epidermal and sebaceous gland homeostasis. We suggest that c-Myc may be activating follicular stem cells either directly or indirectly and that this has important implications for control of the 'hair cycle clock', hair growth and epidermal maintenance.
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c-Myc is a fundamental factor that governs sebaceous gland expansion in vivo.
“A fundamental factor that governs SG expansion in vivo is c-Myc3, 29–31,.”
From Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro (2019) · cites this paper as [30]
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A common human skin tumour is caused by activating mutations in β-catenin
Chan, E., Gat, U., McNiff, J. M., & Fuchs, E. (1999) · Nature Genetics · doi:10.1038/7747 · Cited by 612 · see citing works
Deregulated expression of c-Myc depletes epidermal stem cells
Waikel, R. L., Kawachi, Y., Waikel, P. A., Wang, X.-J., & Roop, D. R. (2001) · Nature Genetics · doi:10.1038/88889 · Cited by 318 · see citing works
Van Mater, D., Kolligs, F. T., Dlugosz, A. A., & Fearon, E. R. (2003) · Genes & Development · doi:10.1101/gad.1076103 · Cited by 263 · see citing works
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Lactate dehydrogenase activity drives hair follicle stem cell activation
Flores, A., Schell, J., Krall, A. S., Jelinek, D., Miranda, M., Grigorian, M., Braas, D., White, A. C., Zhou, J. L., Graham, N. A., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3575 · Cited by 301 · see citing works
MYC in mammalian epidermis: how can an oncogene stimulate differentiation?
Watt, F. M., Frye, M., & Benitah, S. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2328 · Cited by 157 · see citing works
Blimp1+ cells generate functional mouse sebaceous gland organoids in vitro
Feldman, A., Mukha, D., Maor, I. I., Sedov, E., Koren, E., Yosefzon, Y., Shlomi, T., & Fuchs, Y. (2019) · Nature Communications · doi:10.1038/s41467-019-10261-6 · Cited by 52 · see citing works
Janghorban, M., Langer, E. M., Wang, X., Zachman, D., Daniel, C. J., Hooper, J., Fleming, W. H., Agarwal, A., & Sears, R. C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0188910 · Cited by 19 · see citing works
- Authors
- Bull, J. J., Pelengaris, S., Hendrix, S., Chronnell, C. M. T., Khan, M., & Philpott, M. P.
- Affiliations
- Queen Mary University of London (GB)
- Corresponding author
- Philpott, M.P.
- Venue
- British Journal of Dermatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06
- Volume
- 152
- Issue
- 6
- Pages
- 1125-1133
- ISSN
- 0007-0963 (ISSN-L)
- 1365-2133
- OpenAlex
- W1971005855
- Cited by
- 32
- References
- 3
- Citations by year
- 2026: 2 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- British Journal of Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leverhulme Trust
- Biotechnology and Biological Sciences Research Council
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
- Keywords
- c-Myc, hair cycle, hair follicle, epidermal keratinocytes, epithelial cell proliferation, hair follicle stem cells, transgenic mice, oncoprotein, skin homeostasis
- MeSH terms
- Animals, Epidermis, Estrogen Antagonists, Hair, Humans, Immunohistochemistry, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Scalp, Sebaceous Glands, Tamoxifen, Biomarkers, Gene Expression, Genes, myc, Proto-Oncogene Proteins c-myc, Hair Follicle, Ki-67 Antigen, In Situ Nick-End Labeling, Cell Proliferation, Mice
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