High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene

The gene encoding AIB1, an estrogen receptor coactivator, is amplified in a subset of human breast cancers. Here we show that overexpression of AIB1 in transgenic mice (AIB1-tg) leads to mammary hypertrophy, hyperplasia, abnormal postweaning involution, and the development of malignant mammary tumors. Tumors are also increased in other organs, including the pituitary and uterus. AIB1 overexpression increases mammary IGF-I mRNA and serum IGF-I protein levels. In addition, IGF-I receptor and downstream signaling molecules are activated in primary mammary epithelial cells and mammary tumor cells derived from AIB1-tg mice. Knockdown of AIB1 expression in cultured AIB1-tg mammary tumor cells leads to reduced IGF-I mRNA levels and increased apoptosis, suggesting that an autocrine IGF-I loop underlies the mechanism of AIB1-induced oncogenesis.

Medienart:

Artikel

Erscheinungsjahr:

2004

Erschienen:

2004

Enthalten in:

Zur Gesamtaufnahme - volume:6

Enthalten in:

Cancer cell - 6(2004), 3 vom: 15. Sept., Seite 263-74

Sprache:

Englisch

Beteiligte Personen:

Torres-Arzayus, Maria I [VerfasserIn]
Font de Mora, Jaime [VerfasserIn]
Yuan, Jing [VerfasserIn]
Vazquez, Francisca [VerfasserIn]
Bronson, Roderick [VerfasserIn]
Rue, Montserrat [VerfasserIn]
Sellers, William R [VerfasserIn]
Brown, Myles [VerfasserIn]

Themen:

67763-96-6
Acetyltransferases
EC 2.3.1.-
EC 2.3.1.48
EC 2.7.11.26
Glycogen Synthase Kinase 3
Histone Acetyltransferases
Insulin-Like Growth Factor I
Journal Article
NCOA3 protein, human
Ncoa3 protein, mouse
Nuclear Receptor Coactivator 3
Oncogene Proteins
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Trans-Activators

Anmerkungen:

Date Completed 02.11.2004

Date Revised 10.03.2022

published: Print

Citation Status MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM150548052