title: Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.
abstract: BACKGROUND
  Activator protein 2 gamma (AP-2gamma) 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-2gamma 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-2gamma binding sites on genomic DNA from human breast cancer cell line MDA-MB-453.
  
  
  RESULTS
  20 novel DNA fragments proximal to potential AP-2gamma 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-2gamma 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-2gamma. Decreased expression and overexpression of AP-2gamma in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2gamma directly regulates them.
  
  
  CONCLUSIONS
  This suggested that AP-2gamma 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.
authors: Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, PR China. pdheailan@126.com
authors: He
authors: H
authors: Ailan
authors: Xiao
authors: X
authors: Xiangwen
authors: Ren
authors: R
authors: Daolong
authors: Gan
authors: G
authors: Lu
authors: Ding
authors: D
authors: Xiaofeng
authors: Qiao
authors: Q
authors: Xi
authors: Hu
authors: H
authors: Xingwang
authors: Liu
authors: L
authors: Rushi
authors: Zhang
authors: Z
authors: Jian
authors: Xiang
authors: X
authors: Shuanglin
mesh_terms: D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015820:Cadherins / Q000737:chemistry / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D011485:Protein Binding; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000235:genetics; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D000099175:Heparanase
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D015815:Cell Adhesion Molecules; D005966:Glucuronidase; D007136:Immunoglobulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D050656:Transcription Factor AP-2; D000099175:Heparanase; C050361:CDH2 protein, human; C482101:IGSF11 protein, human; C508053:ERBB2 protein, human