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Abstract

SummaryThe 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.

miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy

“…It is well-understood that melanoma progression is associated with loss of expression of AP-2 proteins, and this correlates with poor prognosis and advanced stages of the disease [ 30 , 31 ]. Loss or deletions of genomic loci encoding for TFAP2 family members were found in some, but not all, melanomas, suggesting involvement of other mechanisms for control of gene expression [ 32 ]. It is known that elimination of TFAP2A from non-metastatic primary melanoma cells increases their malignancy while re-expression abrogates it, by controlling transcription of genes such as MCAM-MUC18 , MMP2 , PAR1 , VEGF , BCL2 , CDKN1A /p21, E-cadherin and KIT [ 33 - 35 ].…”

TFAP2B overexpression contributes to tumor growth and a poor prognosis of human lung adenocarcinoma through modulation of ERK and VEGF/PEDF signaling

“…TFAP2B belongs to the TFAP2 family. TFAP2A and TFAP2C have been implicated in cancer progression, vascularization, metastasis, and recurrence [ 31 - 33 ]. However, the biological roles and clinical significance of TFAP2B and its precise molecular mechanisms in lung cancer have not been reported.…”

Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions

“…The shared TFs were MYC, ETS1, and TFAP2A, with, MYC [ 29 ] and ETS1 [ 30 ] being reported to be lung cancer-related TFs. Although TFAP2A has not been explicitly reported to be associated with lung cancer, it has been associated with the generation of a variety of tumors [ 31 , 32 ]. The two 4-node subnets (crosstalk and joint) have more common TFs, namely TP53 [ 33 ], SP1 [ 34 ], E2F4 [ 35 ], NFKB1 [ 36 ], and MYB [ 37 ].…”