Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells.
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.
Ailan
He
H
Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, PR China. pdheailan@126.com
Xiangwen
Xiao
X
Daolong
Ren
R
Lu
Gan
G
Xiaofeng
Ding
D
Xi
Qiao
Q
Xingwang
Hu
H
Rushi
Liu
L
Jian
Zhang
Z
Shuanglin
Xiang
X
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
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