Cargando…

CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies

The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously...

Descripción completa

Detalles Bibliográficos
Autores principales: Brożyna, Anna A., Jochymski, Cezary, Janjetovic, Zorica, Jóźwicki, Wojciech, Tuckey, Robert C., Slominski, Andrzej T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227257/
https://www.ncbi.nlm.nih.gov/pubmed/25334067
http://dx.doi.org/10.3390/ijms151019000
_version_ 1782343769825214464
author Brożyna, Anna A.
Jochymski, Cezary
Janjetovic, Zorica
Jóźwicki, Wojciech
Tuckey, Robert C.
Slominski, Andrzej T.
author_facet Brożyna, Anna A.
Jochymski, Cezary
Janjetovic, Zorica
Jóźwicki, Wojciech
Tuckey, Robert C.
Slominski, Andrzej T.
author_sort Brożyna, Anna A.
collection PubMed
description The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.
format Online
Article
Text
id pubmed-4227257
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-42272572014-11-12 CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies Brożyna, Anna A. Jochymski, Cezary Janjetovic, Zorica Jóźwicki, Wojciech Tuckey, Robert C. Slominski, Andrzej T. Int J Mol Sci Article The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)(2)D3) homeostasis. Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities. Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas. Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases. In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis. The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas. With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases. Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity. Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes. Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival. In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development. MDPI 2014-10-20 /pmc/articles/PMC4227257/ /pubmed/25334067 http://dx.doi.org/10.3390/ijms151019000 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Brożyna, Anna A.
Jochymski, Cezary
Janjetovic, Zorica
Jóźwicki, Wojciech
Tuckey, Robert C.
Slominski, Andrzej T.
CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title_full CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title_fullStr CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title_full_unstemmed CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title_short CYP24A1 Expression Inversely Correlates with Melanoma Progression: Clinic-Pathological Studies
title_sort cyp24a1 expression inversely correlates with melanoma progression: clinic-pathological studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227257/
https://www.ncbi.nlm.nih.gov/pubmed/25334067
http://dx.doi.org/10.3390/ijms151019000
work_keys_str_mv AT brozynaannaa cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies
AT jochymskicezary cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies
AT janjetoviczorica cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies
AT jozwickiwojciech cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies
AT tuckeyrobertc cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies
AT slominskiandrzejt cyp24a1expressioninverselycorrelateswithmelanomaprogressionclinicpathologicalstudies