AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

被引:51
作者
Perissi, V
Menini, N
Cottone, E
Capello, D
Sacco, M
Montaldo, F
De Bortoli, M
机构
[1] Inst Canc Res & Treatment, I-10060 Candiolo, Italy
[2] Univ Turin, Dept Anim & Human Biol, I-10124 Turin, Italy
关键词
ERBB2; oestrogen repression; AP-2; ER;
D O I
10.1038/sj.onc.1203303
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transcription of the ERBB2 oncogene is repressed by oestrogen in human breast cancer cells. We show that a 218 bp fragment of the human ERBB2 gene promoter is responsive to oestrogen in transient transfection in ZR75.1 and SKBR.3 cells when the oestrogen receptor is expressed. Deletion analysis of this fragment shows that a sequence located at the 5' end, which is known to mediate ERBB2 overexpression in breast cancer, is also responsible for the oestrogen response. This sequence binds AP-2 transcription factors and appears functionally identical to an element of the oestrogen-dependent enhancer described in the first intron of human ERBB2, We observed that oestrogen treatment down-regulates expression of AP-2 proteins but does not affect the DNA binding activity of AP-2. Constitutive expression of AP-2 beta or AP-2 gamma, but not AP-2 alpha, abrogates the estrogenic repression. Our results demonstrate that AP-2 transcription factors are implicated in the oestrogenic regulation of ERBB2 gene expression and suggest a complex interplay involving the different AP-2 isoforms and other unidentified factors.
引用
收藏
页码:280 / 288
页数:9
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