Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways

摘要: Overexpression of hepatocyte growth factor (HGF), also called scatter (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cells can produce HGF that acts in a paracrine as well an autocrine manner. Therefore, putative targets therapy. To explore HGF/c-Met signaling cancer, we have generated transgenic mice expressing specifically mammary epithelium under the transcriptional control whey acidic protein (WAP) gene promoter. WAP-HGF females developed hyperplastic ductal trees multifocal invasive tumors after several pregnancies, some which progressed to lung metastases. Tumors produced displayed phosphorylated c-Met, correlated increased Akt c-myc activation. A high rate, demonstrated by Ki67 nuclear antigen staining, lack progesterone were characteristic tumors. Immunohistochemical analysis revealed areas osteopontin (Opn) expression metastases agreement previously reported role Opn growth. We suggest these may serve new model evaluation effects unscheduled cancer.