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, Pamela 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
StatePublished - Jun 13 2000

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Melanoma
Messenger RNA
Skin
Proteins
Neoplasms
Transcription Factor AP-2
Monosomy
Chromosomes, Human, Pair 6
Loss of Heterozygosity
Tumor Suppressor Genes
Microsatellite Repeats
In Situ Hybridization
Down-Regulation
Chromosomes
Cell Line
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

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.
Karjalainen, J. M. ; Kellokoski, J. K. ; Mannermaa, A. J. ; Kujala, H. E. ; Moisio, K. I. ; Mitchell, Pamela J. ; Eskelinen, M. J. ; Alhava, E. M. ; Kosma, V. M. / Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma. In: British Journal of Cancer. 2000 ; Vol. 82, No. 12. pp. 2015-2021.
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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.",
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Karjalainen, JM, Kellokoski, JK, Mannermaa, AJ, Kujala, HE, Moisio, KI, Mitchell, PJ, Eskelinen, MJ, Alhava, EM & Kosma, VM 2000, 'Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma', British Journal of Cancer, vol. 82, no. 12, pp. 2015-2021.

Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma. / Karjalainen, J. M.; Kellokoski, J. K.; Mannermaa, A. J.; Kujala, H. E.; Moisio, K. I.; Mitchell, Pamela J.; Eskelinen, M. J.; Alhava, E. M.; Kosma, V. M.

In: British Journal of Cancer, Vol. 82, No. 12, 13.06.2000, p. 2015-2021.

Research output: Contribution to journalArticle

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T1 - Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma

AU - Karjalainen, J. M.

AU - Kellokoski, J. K.

AU - Mannermaa, A. J.

AU - Kujala, H. E.

AU - Moisio, K. I.

AU - Mitchell, Pamela J.

AU - Eskelinen, M. J.

AU - Alhava, E. M.

AU - Kosma, V. M.

PY - 2000/6/13

Y1 - 2000/6/13

N2 - 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.

AB - 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.

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Karjalainen JM, Kellokoski JK, Mannermaa AJ, Kujala HE, Moisio KI, Mitchell PJ et al. Failure in post-transcriptional processing is a possible inactivation mechanism of AP-2α in cutaneous melanoma. British Journal of Cancer. 2000 Jun 13;82(12):2015-2021.