Reference SummaryTorres-Arzayus MI, Cancer Cell 2004 Sep;6(3):263-74

Title

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

Authors

Torres-Arzayus MI; De Mora JF; Yuan J; Vazquez F; Bronson R; Rue M; Sellers WR; Brown M

Journal

Cancer Cell

Volume

6

Issue

3

Year

2004

Pages

263-74

Abstract

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.

Links

J:93548 – Mouse Genome Informatics
15380517 – National Library of Medicine/PubMed

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB/NTac-Tg(MMTV-NCOA3)#Mybr Adrenal gland - Cortex tumor Adrenal gland - Cortex

2

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Connective tissue - Fibroblast fibrosarcoma Connective tissue - Fibroblast

6

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Leukocyte - Monocyte - Macrophage sarcoma Bone

2

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Leukocyte lymphoma Leukocyte

2

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Lung adenocarcinoma Lung

18

FVB/NTac Lung tumor Lung

2.9

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma Mammary gland

48

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - acinar Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - comedo Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - cribriform Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - ductal Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - lobular Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - microacinar Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - papillary Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland adenocarcinoma - solid/comedo Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland cyst - squamous Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland mammary intraepithelial neoplasia (MIN) Mammary gland

high

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland metaplasia - squamous Mammary gland

observed

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Mammary gland tumor Mammary gland

50

FVB/NTac Mammary gland tumor Mammary gland

0

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Muscle - Smooth leiomyosarcoma Uterus

18

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Ovary - Germ cell teratoma Ovary - Germ cell

3

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Pituitary gland adenoma Pituitary gland

42

FVB/NTac Pituitary gland tumor Pituitary gland

1.9

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Skin papilloma Skin

3

FVB/NTac-Tg(MMTV-NCOA3)#Mybr Skin squamous cell carcinoma Skin

1

FVB/NTac-Tg(MMTV-NCOA3)#Mybr (Unspecified organ) tumor (Unspecified organ)

76 - 80

FVB/NTac (Unspecified organ) tumor (Unspecified organ)

4.8