New Perspectives on Melanoma_ The Role of PAX3

New Perspectives on Melanoma The Role of PAX3

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Unformatted text preview: ved in Pax3‐induced cell survival [28,225,226]. BCL2L1 is directly transcriptionally regulated by PAX3, and in rhabdomyosarcoma treatment with PAX3 or BCL2L1 antisense oligonucleotides, individually or in combination, decreases cell viability to a similar extent, suggesting that they lie in the same antiapoptotic pathway [226]. Similarly, BCL2L1 is associated with melanoma cell survival, since its expression correlates with melanoma progression [255,256] and treatment with antisense oligonucleotides resulted in reduction of cell viability [257,258]. However, its expression is observed in naevi and normal skin [255,256] and in melanocytes it also affects cell viability [258]. As expected we have observed positive BCL2L2 staining in all normal skin, naevi and primary melanoma samples analysed. The majority of PAX3‐positive cells in melanomas and naevi samples and melanocytes in normal skin co‐express BCL2L2, at a similar frequency. These results support the potential role of PAX3 as one of many cell survival regulators. The results also indicate that normal melanocytes 70 Chapter III – Medic and Ziman, 2010 might utilise the same cell survival regulatory pathway as melanoma cells, both in the epidermis and in hair follicles. PAX3 in migration The cell adhesion molecule MCAM has been associated with melanoma progression and metastatic potential [259‐262]. Even though MCAM is frequently expressed in naevi [250] its increased expression in melanomas shows significant correlation with poor disease free survival and mortality [250,259‐261,263,264]. Upregulation of MCAM, together with loss of keratinocyte‐dependence, is one of the crucial events that allows melanoma cells to invade the dermis and progress to vertical growth phase (for review see [265]). MCAM can mediate both homotypic adhesion between melanoma cells, promoting local tumour growth, and heterotypic adhesion between melanoma cells and endothelial cells of blood vessels, facilitating metastatic spread [237,262,266]. Pax3‐transfected melanocyte cells show upregulation of MCAM, both at an mRNA and protein level, suggesting that MCAM is a downstream target of Pax3 [121,204]. Our results confirm co‐expression of PAX3 and MCAM in melanomas and naevi, mainly in the cells that form nes...
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This document was uploaded on 03/06/2014 for the course CHEMISTRY 12 at National University of Singapore.

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