Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

Background: Activator protein 2 gamma (AP-2 gamma)is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2 gamma has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. Methods: To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2 gamma binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. Results: 20 novel DNA fragments proximal to potential AP-2 gamma targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2 gamma target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2 gamma. Decreased expression and overexpression of AP-2 gamma in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2 gamma directly regulates them. Conclusion: This suggested that AP-2 gamma can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.