title: Assessing estrogen signaling aberrations in breast cancer risk using genetically engineered mouse models.
abstract: 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.
authors.affiliation: Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. paf3@georgetown.edu
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Furth
authors.forename: M Carla
authors.initials: MC
authors.lastname: Cabrera
authors.forename: Edgar S
authors.initials: ES
authors.lastname: Díaz-Cruz
authors.forename: Sarah
authors.initials: S
authors.lastname: Millman
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Nakles
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005818:Genetic Engineering; D051379:Mice; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D004967:Estrogens