Disease relevance of TFAP2C

• Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis [1].
• PURPOSE: Transcription factor activator protein-2gamma (TFAP2C, AP-2gamma) was reported previously in extraembryonic ectoderm and breast carcinomas but not in the testis [2].
• The ERF-1 transcription factor was previously shown to be involved in the regulation of estrogen receptor (ER) gene transcription in hormonally responsive breast and endometrial carcinomas [3].
• The authors report the identification of 2 cell membrane-permeable compounds that exhibit activity in the ERF1 Redistribution assay and selectively inhibit proliferation of MAPK pathway-dependent malignant melanoma cells at similar potencies (IC(50)=< 5 microM) [4].
• Knockdown of TFAP2C abrogated the mitogenic response to estrogen exposure and decreased hormone-responsive tumor growth of breast cancer xenografts [5].

High impact information on TFAP2C

• Identification of ERF-1 as a member of the AP2 transcription factor family [3].
• Given the central role of ER expression in breast carcinoma biology, ERF-1 is likely to regulate expression of a set of genes characteristic of the hormonally-responsive breast cancer phenotype [3].
• ERF-1 protein was purified from the ER-positive breast carcinoma cell line, MCF7, utilizing ion exchange and DNA affinity chromatography [3].
• This region contains two binding sites for a protein, estrogen receptor factor 1 (ERF-1), which is expressed in ER-positive breast carcinomas [6].
• A concatenated ERF-1 binding site probe identified a 30,000-Da protein [6].

Biological context of TFAP2C

• CITED2 interacted with the dimerization domain of TFAP2C, which is highly conserved in TFAP2A/B [7].
• In the present study, we report the complete sequence determination of the human TFAP2C gene encoding the AP-2gamma transcription factor plus the mapping of the transcription start site used in breast tumour-derived cells [8].
• In cotransfection assays in rat pituitary GC cells, AP2 gamma transactivated the enhancer via this region [9].
• Proteomic identification of AP2 gamma as a rat placental lactogen II trophoblast cell-specific enhancer binding protein [9].

Anatomical context of TFAP2C

• Low-level ERF-1 expression was detected in normal human mammary epithelial cells [6].
• Several peptides of AP2 gamma, a key trophoblast cell-specific transcription factor, were identified [9].
• Chromatin immunoprecipitation assays confirmed AP2 gamma occupancy of the enhancer region in situ in the nuclei of Rcho giant cells [9].

Associations of TFAP2C with chemical compounds

• Reduced disease-free survival, but not reduced overall survival, was associated with high expression of TOP1 (P = 0.035) and TFAP2C (P = 0.035) [1].

Other interactions of TFAP2C

• In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation [10].
• Here we show that these mutations significantly reduce the capacity of CITED2 to transrepress HIF1A, and that the p.Ser170_Gly178del mutation significantly diminishes TFAP2C coactivation [11].
• Other genes that were highly ranked for their expression in ACC were those encoding the transcription factors SOX4 and AP-2 gamma, the latter of which also was overexpressed in ACC relative to 175 other carcinomas from 10 anatomical sites that we had previously profiled [12].

Analytical, diagnostic and therapeutic context of TFAP2C

• By gel-shift analysis, in vitro synthesized ERF-1 comigrates with MCF7 native ERF-1 complex and demonstrates identical sequence binding specificity as native ERF-1 [3].

References