title: Analysis of the status of the novel estrogen receptor α (ERα) coactivator p72 in endometrial cancer and its cross talk with erbB-2 in the transactivation of ERα.
abstract: To determine how estrogens are involved in the growth of endometrial cancer with varying degrees of differentiation, we investigated the status of p72, a novel specific coactivator for estrogen receptor α (ERα) activation function-1 (AF-1), AIB1, a steroid receptor coactivator amplified in breast cancer 1, erbB-2, a receptor tyrosine kinase, and ERα in endometrial cancer. Gene expression of ERα, p72, AIB1 and erbB-2 was measured in 26 samples of primary endometrial cancers by real-time RT-PCR, and their in vivo cellular effects on the transactivation function of ERα were examined by a transient expression assay. The mRNA levels of erbB-2 increased and those of ERα, p72 and AIB1 decreased with the loss of histological differentiation. Transient expression of p72, AIB1 and erbB-2 in human embryonic kidney 293T cells led to a synergistic promotion of the transactivation function of ERα in the presence of 17α-estradiol or 4-hydroxytamoxifen, an ERα AF-1 agonist/AF-2 antagonist, as a ligand. In conclusion, estrogen action through ERα AF-1 might be exerted by the increased expression of the coactivators p72 and AIB1, together with cross talk between erbB-2 and p72, to accelerate the transactivation of ERα AF-1 in endometrial cancer. These findings also suggest that the cooperative transactivation of ERα AF-1 by the overexpression of p72, AIB1 and erbB-2 might be involved in tamoxifen-stimulated growth of endometrial cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Michiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yano
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Oishi
authors.forename: Osamu
authors.initials: O
authors.lastname: Wada-Hiraike
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Oda
authors.forename: Takeo
authors.initials: T
authors.lastname: Minaguchi
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yasugi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Kato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani