PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).

<h4>Background</h4>Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. B...

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Autores principales:	Sandra Medic, Mel Ziman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80e739ae8f854e518e4371a9dfae60a6
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spelling	oai:doaj.org-article:80e739ae8f854e518e4371a9dfae60a62021-11-25T06:24:22ZPAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).1932-620310.1371/journal.pone.0009977https://doaj.org/article/80e739ae8f854e518e4371a9dfae60a62010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20421967/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized) refer to the corresponding mouse and human protein.<h4>Methodology and principal findings</h4>PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype.<h4>Conclusions and significance</h4>Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic lesions in which PAX3 expression is prominent.Sandra MedicMel ZimanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e9977 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sandra Medic Mel Ziman PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
description	<h4>Background</h4>Cutaneous Malignant Melanoma is an aggressive form of skin cancer, arising in cutaneous melanocytes. The transcription factor PAX3 regulates melanocyte specification from neural crest cells during development but expression in differentiated melanocytes is uncertain. By contrast it is frequently found in melanomas and naevi and is a marker for melanoma staging and detection. In this study we analysed the expression of PAX3 across the spectrum of melanocytic cells, from normal melanocytes to cells of benign and malignant lesions to better assess its function in these various tissues. Pax3 and PAX3 (italicized) refer to the mouse and human gene, respectively; whereas Pax3 and PAX3 (non-italicized) refer to the corresponding mouse and human protein.<h4>Methodology and principal findings</h4>PAX3 expression was analysed by immunohistochemistry and qRT-PCR. Immunofluorescence was used for co-expression with differentiation, migration and survival markers. As expected PAX3 expression was observed in naevi and melanoma cells. It was also found in melanocytes of normal skin where it co-expressed with melanocyte markers, MITF and MLANA. Co-expression with its downstream target, antiapoptotic factor BCL2L1 confirms PAX3 as a cell survival regulator. PAX3 was also co-expressed with melanoma cell migration marker MCAM in dermal naevi and melanoma cell nests, but this downstream target of PAX3 was not present in normal epidermal melanocytes, suggesting differential roles for PAX3 in normal epidermal melanocytes and melanoma cells. Most interestingly, a proportion of PAX3-positive epidermal melanocytes in normal skin show HES1 and Ki67 co-expression, indicating their less differentiated proliferative phenotype.<h4>Conclusions and significance</h4>Our results suggest that a previously identified role for PAX3, that of regulator of an undifferentiated plastic state, may operate in melanocytes of normal skin. This role, possibly required for cellular response to environmental stimuli, may contribute to formation and development of melanocytic lesions in which PAX3 expression is prominent.
format	article
author	Sandra Medic Mel Ziman
author_facet	Sandra Medic Mel Ziman
author_sort	Sandra Medic
title	PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
title_short	PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
title_full	PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
title_fullStr	PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
title_full_unstemmed	PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
title_sort	pax3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/80e739ae8f854e518e4371a9dfae60a6
work_keys_str_mv	AT sandramedic pax3expressioninnormalskinmelanocytesandmelanocyticlesionsnaeviandmelanomas AT melziman pax3expressioninnormalskinmelanocytesandmelanocyticlesionsnaeviandmelanomas
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PAX3 expression in normal skin melanocytes and melanocytic lesions (naevi and melanomas).

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