New Perspectives on Melanoma_ The Role of PAX3

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Unformatted text preview: itive epidermal melanocytes in normal skin show HES1 and Ki67 co‐expression, indicating their less differentiated proliferative phenotype. Conclusions and Significance: 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. 53 Chapter III – Medic and Ziman, 2010 Introduction Cutaneous Malignant Melanoma is a highly aggressive form of skin cancer, thought to be derived from cutaneous melanocytes or melanoblasts. Its aggressiveness is attributed to frequent metastasis and high drug resistance. Intensive research into the mechanisms regulating melanoma tumourigenesis has included investigation of the factors and pathways of normal melanocyte development and function. One key factor that regulates melanocyte development from neural crest derived progenitor cells is the transcriptional factor PAX3. PAX3 is very frequently expressed in melanomas and naevi [21,23‐25,73,151]. In fact, PAX3 has been identified as a significant marker for melanoma staging [22,26] and for detection of circulating melanoma cells [22]. It has also been identified as an immunogenic protein in melanomas [157‐159], with several epitopes able to induce the host’s immune response ‐ stimulation of the immune response against PAX3‐expressing tumour cells results in tumour growth suppression [157,159]. PAX3 is a member of the PAX family of transcription factors which are highly conserved throughout phylogeny. All play a crucial role in embryogenesis but are also implicated in tumourigenesis [13‐15,52,53,169,209]. Although PAX3 is recognised as a key embryonic regulator of melanocyte specification and development, its expression and function in differentiated epidermal melanocytes of adult human skin is largely unexplored and its role in melanoma remains unclear [1]. Pax3 starts its expression in early embryos, in neural crest precursor c...
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