Use of MMTV-Wnt-1 transgenic mice for studying the genetic basis of breastcancer

Wnt-1 was first identified as a protooncogene activated by viral insertion in mouse mammary tumors. Transgenic expression of this gene using a mouse m ammary tumor virus LTR enhancer causes extensive ductal hyperplasia early i n life and mammary adenocarcinomas in approximately 50% of the female trans genic (TG) mice by 6 months of age. Metastasis to the lung and proximal lym ph nodes is rare at the time tumors are detected but frequent after the rem oval of the primary neoplasm, The potent mitogenic effect mediated by Wnt-1 expression does not require estrogen stimulation; tumors form after an inc reased latency in estrogen receptor alpha-null mice. Several genetic lesion s, including inactivation of p53 and over-expression of Fgf-3, collaborate with Wnt-1 in leading to mammary tumors, but loss of Sky and inactivation o f one allele of Rb do not affect the rate of tumor formation in Wnt-1 TG mi ce.