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. 2000 May 18;82(12):2015–2021. doi: 10.1054/bjoc.2000.1145

Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2 α in cutaneous melanoma

J M Karjalainen 1,6, J K Kellokoski 3,4,6, A J Mannermaa 5, H E Kujala 5, K I Moisio 6, P J Mitchell 7, M J Eskelinen 1, E M Alhava 1, V M Kosma 2,6
PMCID: PMC2363258  PMID: 10864211

Abstract

The loss of transcription factor AP-2α expression has been shown to associate with tumourigenicity of melanoma cell lines and poor prognosis in primary cutaneous melanoma. Altogether these findings suggest that the gene encoding AP-2α (TFAP2A) acts as a tumour suppressor in melanoma. To learn more of AP-2α’s down-regulation mechanisms, we compared the immunohistochemical AP-2α protein expression patterns with the corresponding mRNA expression detected by in situ hybridization in 52 primary melanomas. Of the 25 samples with AP-2α protein negative areas, 16 (64%) expressed mRNA throughout the consecutive section. Nine specimens (36%) contained equally mRNA- and protein-negative areas, suggesting that the loss of AP-2α protein associated with lack of the mRNA transcript. The highly AP-2α protein-positive tumours (n = 27) were concordantly mRNA positive in 25 (92.6%) cases. Thirteen primary tumours were further analysed using microsatellite markers D6S470 and D6S263 for loss of heterozygosity (LOH) of a locus harbouring TFAP2A. LOHs or chromosome 6 monosomy were found in four out of five (80%) informative AP-2α mRNA- and protein-negative tumour areas, but also within five out of 13 (38%) informative AP-2α mRNA-positive tumour areas. This chromosome region is thus suggestive of harbouring a putative tumour suppressor gene of cutaneous melanoma, but this referring specifically to TFAP2A could not be completely verified in this analysis. We conclude that a failure in post-transcriptional processing of AP-2α is a possible inactivation mechanism of AP-2α in cutaneous melanoma. Copyright 2000 Cancer Research Campaign© 2000 Cancer Research Campaign

Keywords: cutaneous melanoma, gene expression, AP-2, mRNA in situ hybridization, loss of heterozygosity

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Selected References

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