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

Abstract

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 ®rst intron of human ERBB2. We observed that oestrogen treatment down-regulates expression of AP-2 proteins but does not a ect the DNA binding activity of AP-2. Constitutive expression of AP2b or AP-2g, but not AP-2a, 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 di erent AP-2 isoforms and other unidenti®ed factors. Oncogene (2000) 19, 280 ± 288.

Drug-inducible and simultaneous regulation of endogenous genes by single-chain nuclear receptor-based zinc-finger transcription factor gene switches

“…Tamoxifen, which in an endogenous ER antagonist, may be affecting AP-2 regulation of ErbB2 transcription. 28 For the RE and RLE iTF ZF s, there is a retinoic acid-responsive element close to the CD54-31- ICAM-1) expression. CD54-31-scER-, -RE-and -RLE inducible zincfinger transcription factors (iTF ZF s) with either -VP64 and -KRAB (Krü ppel-associated box) domains were retrovirally expressed in HeLa cells for 2 days.…”

The role of BST‐2/Tetherin in host protection and disease manifestation

“…Reduction in BST‐2 expression upon TGF‐β treatment correlates with enhanced AP2 binding to the BST‐2 promoter 123. AP2 is a transcription factor involved in repression of promoter sequences of at least one oncogene ERBB2 159. These findings suggest that in breast cancer cells, there is a progressive loss of TGF‐β signaling responsiveness that may result in aberrant BST‐2 overexpression.…”

ERBB2 influences the subcellular localization of the estrogen receptor in tamoxifen-resistant MCF-7 cells leading to the activation of AKT and RPS6KA2

“…Studies have shown that E 2 -bound ESR1 represses ERBB2 transcription by competing for transcription factors such as NCOA1 (Bates & Hurst 1997, Perissi et al 2000. However, tamoxifen-bound ESR1 recruits NCOR allowing ERBB2 transcription to be activated (Newman et al 2000).…”