Transcription of the ERBB2 oncogene is repressed by oestrogen in human brea
st cancer cells. We show that a 218 bp fragment of the human ERBB2 gene pro
moter is responsive to oestrogen in transient transfection in ZR75.1 and SK
BR.3 cells when the oestrogen receptor is expressed. Deletion analysis of t
his 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 app
ears functionally identical to an element of the oestrogen-dependent enhanc
er described in the first intron of human ERBB2, We observed that oestrogen
treatment down-regulates expression of AP-2 proteins but does not affect t
he 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 resu
lts demonstrate that AP-2 transcription factors are implicated in the oestr
ogenic regulation of ERBB2 gene expression and suggest a complex interplay
involving the different AP-2 isoforms and other unidentified factors.