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

J. M. Karjalainen, J. K. Kellokoski, A. J. Mannermaa, H. E. Kujala, K. I. Moisio, P. J. Mitchell, M. J. Eskelinen, E. M. Alhava, V. M. Kosma

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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. (C) 2000 Cancer Research Campaign.

Original languageEnglish (US)
Pages (from-to)2015-2021
Number of pages7
JournalBritish Journal of Cancer
Volume82
Issue number12
Publication statusPublished - Jun 13 2000

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Karjalainen, J. M., Kellokoski, J. K., Mannermaa, A. J., Kujala, H. E., Moisio, K. I., Mitchell, P. J., ... Kosma, V. M. (2000). Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma. British Journal of Cancer, 82(12), 2015-2021.