Expression of the vitamin D–activating enzyme 1α-hydroxylase (CYP27B1) decreases during melanoma progression
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1α-Hydroxylase (CYP27B1), the enzyme responsible for the synthesis of the biologically active form of vitamin D (1,25(OH)(2)D(3)), is expressed in the skin. To assess the correlation between progression of melanocytic tumors and CYP27B1, we analyzed its expression in 29 benign nevi, 75 primary cutaneous melanomas, 40 metastases, and 4 re-excision and 6 normal skin biopsies. Immunoreactivity for CYP27B1 was significantly lower in the vertical growth phase and metastatic melanomas (0.6 and 0.5 arbitrary units, respectively) in comparison with nevi and radial growth phase tumors (1.2 and 1.1 arbitrary units, respectively); and expression was reduced in more advanced lesions (Clark levels III-V, Breslow thickness ≥2.1 mm; 0.8 and 0.7 arbitrary units, respectively). There was an inverse correlation between CYP27B1 and Ki-67 expression. Furthermore, CYP27B1 expression was reduced in primary melanomas that created metastases in comparison with non-metastasizing melanomas. Reduced CYP27B1 expression in radial growth phase was related to shorter overall survival (810 versus 982 versus 1151 days in melanomas with absent, low, and high CYP27B1 immunoreactivity), and low CYP27B1 expression in radial growth phase and vertical growth phase was related to shorter disease-free survival (114 versus 339 versus 737 days and 129 versus 307 versus 737 days, respectively, in melanomas with absent, low, and high CYP27B1). Also, CYP27B1 expression was inversely related to melanin in melanoma cells in vivo and melanoma cells cultured in vitro. Thus, reduction of CYP27B1 correlates with melanoma phenotype and behavior, and its lack affects the survival of melanoma patients, indicating a role in the pathogenesis and progression of this cancer.
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VDR and CYP27B1 expression decrease during melanoma progression, and melanization and melanogenesis negatively affect overall and stage III disease survival.
“expression of the VDR and CYP27B1 decreased during melanoma progression, and melanization and melanogenesis negatively affected both overall- and stage III disease-survival”
From The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions (2014) · cites this paper as [80]
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Self-citationHydroxylation of CYP11A1-derived products of vitamin D3 metabolism by human and mouse CYP27B1
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- Authors
- Brożyna, A. A., Jóźwicki, W., Janjetovic, Z., & Slominski, A. T.
- Affiliations
- Nicolaus Copernicus University (PL)
- University of Tennessee Health Science Center (US)
- Corresponding author
- Slominski, Andrzej T.
- Venue
- Human Pathology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 44
- Issue
- 3
- Pages
- 374-387
- ISSN
- 0046-8177 (ISSN-L)
- PMC
- PMC3529817
- OpenAlex
- W2154250040
- Cited by
- 70
- References
- 39
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 4 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 3 · 2012: 1
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Pathology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR052190, R01AR056666)
- Topics
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- CYP27B1, vitamin D metabolism, cutaneous melanoma, melanoma progression, metastasis, radial growth phase, vertical growth phase, Clark level, Breslow thickness, Ki-67, melanin, overall survival, disease-free survival, melanocytic nevi
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cells, Cultured, Humans, Male, Melanins, Melanoma, Middle Aged, Nevus, Pigmented, Skin, Skin Neoplasms, Vitamin D, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Signal Transduction, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Neoplastic, Receptors, Calcitriol, Disease Progression, Disease-Free Survival, Cell Line, Tumor, Cell Proliferation, Young Adult
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