Assessing estrogen signaling aberrations in breast cancer risk using genetically engineered mouse models
Article first published online: 27 JUL 2011
© 2011 New York Academy of Sciences.
Annals of the New York Academy of Sciences
Volume 1229, Nutrition and Physical Activity in Aging, Obesity, and Cancer pages 147–155, July 2011
How to Cite
Furth, P. A., Cabrera, M. C., Díaz-Cruz, E. S., Millman, S. and Nakles, R. E. (2011), Assessing estrogen signaling aberrations in breast cancer risk using genetically engineered mouse models. Annals of the New York Academy of Sciences, 1229: 147–155. doi: 10.1111/j.1749-6632.2011.06086.x
- Issue published online: 27 JUL 2011
- Article first published online: 27 JUL 2011
- breast cancer;
- mouse models;
- estrogen signaling;
Aberrations in estrogen signaling increase breast cancer risk. Molecular mechanisms that impact breast cancer initiation, promotion, and progression can be investigated using genetically engineered mouse models. Increasing estrogen receptor alpha (ERα) expression levels twofold is sufficient to initiate and promote breast cancer progression. Initiation and promotion can be increased by p53 haploinsufficiency and by coexpressing the nuclear coactivators amplified in breast cancer 1 (AIB1) or the splice variant AIB1Δ3. Progression to invasive cancer is found with coexpression of these nuclear coactivators as well as following a single dose of 7,12-dimethylbenz(a)anthracene. Loss of signal transducer and activator of transcription 5a reduces the prevalence of initiation and promotion but does not protect from invasive cancer development. Cyclin D1 loss completely interrupts mammary epithelial proliferation and survival when ERα is overexpressed. Loss of breast cancer gene 1 increases estrogen signaling and cooperates with ERα overexpression in initiation, promotion, and progression of mammary cancer.