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


RESULTS
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.


CONCLUSIONS
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.
Medic
Sandra
S
School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
Ziman
Mel
M
D015415:Biomarkers; D002465:Cell Movement; D002470:Cell Survival; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000737:chemistry*; D008545:Melanoma / Q000737:chemistry*; D009506:Nevus / Q000737:chemistry*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis* / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000473:pathology
D015415:Biomarkers; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors