PAX3 is expressed in human melanomas and contributes to tumor cell survival.
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.
Scholl
F A
FA
Department of Pediatrics, University of Zurich, Switzerland.
Kamarashev
J
J
Murmann
O V
OV
Geertsen
R
R
Dummer
R
R
Schäfer
B W
BW
D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009367:Neoplasm Staging; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C068686:Pax3 protein, mouse