Genetically engineered ERα-positive breast cancer mouse models.
The majority of human breast cancers are estrogen receptor-positive (ER+), but this has proven challenging to model in genetically engineered mice. This review summarizes information on 21 mouse models that develop ER+ mammary cancer. Where available, information on cancer pathology and gene expression profiles is referenced to assist in understanding which histological subtype of ER+ human cancer each model might represent. ESR1, CCDN1, prolactin, TGFα, AIB1, ESPL1, and WNT1 overexpression, PIK3CA gain of function, as well as loss of P53 (Trp53) or STAT1 are associated with ER+ mammary cancer. Treatment with the PPARγ agonist efatutazone in a mouse with Brca1 and p53 deficiency and 7,12-dimethylbenz(a)anthracene exposure in combination with an activated myristoylated form of AKT1 also induce ER+ mammary cancer. A spontaneous mutant in nude mice that develops metastatic ER+ mammary cancer is included. Age of cancer development ranges from 3 to 26 months and the percentage of cancers that are ER+ vary from 21 to 100%. Not all models are characterized as to their estrogen dependency and/or response to anti-hormonal therapy. Strain backgrounds include C57Bl/6, FVB, BALB/c, 129S6/SvEv, CB6F1, and NIH nude. Most models have only been studied on one strain background. In summary, while a range of models are available for studies of pathogenesis and therapy of ER+ breast cancers, many could benefit from further characterization, and opportunity for development of new models remains.
Departments of Oncology Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road NW, Research Building, Room 520A, Washington, District of Columbia 20057, USA.
Sarah A
SA
Dabydeen
Priscilla A
PA
Furth
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000517:prevention & control*; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice
D047628:Estrogen Receptor alpha
breast; carcinoma; estrogen receptor; mammary gland; pathogenesis