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PAX3 Is Expressed in Human Melanomas and Contributes to Tumor Cell Survival¹

Division of Clinical Chemistry and Biochemistry, Department of Pediatrics, University of Zurich [F. A. S., O. V. M., B. W. S.], Department of Dermatology, University Hospital [J. K., R. G., R. D.], and Medica, Department of Molecular Diagnostics [R. G.], CH-8032 Zurich, Switzerland

Deregulated expression of the transcription factor PAX3 was observed previously in several tumors like rhabdomyosarcoma and Ewing’s sarcoma. Because PAX3 expression is also found in pluripotent neural crest cells, we investigated whether melanomas, tumors derived mostly from cutaneous intraepidermal melanocytes, might show deregulated PAX3 expression. Using a specific and sensitive reverse transcription-PCR, we detected PAX3 mRNA in 77% (27 of 35) of primary cultured melanomas. These results could be confirmed by direct in situ hybridization on the corresponding tissue sections where PAX3 expression was unambiguously confined to tumor cells and not detected in surrounding normal tissue, normal skin sections, or sections of benign lesions. Furthermore, down-regulation of PAX3 expression achieved through a specific antisense oligonucleotide-based treatment resulted in >70% of dead cells specifically in PAX3-positive melanomas. Annexin V staining confirmed that primary melanoma cells underwent apoptosis after treatment. These experiments suggest that in situ hybridization of PAX3 on paraffin-embedded tissue may represent a novel means to identify melanoma cell lesions, which appear to become dependent on expression of this deregulated transcription factor.

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