Insertional mutagenesis identifies a member of the Wnt gene family as a candidate oncogene in the mammary epithelium of int-2/Fgf-3 transgenic mice.

摘要: Abstract Transgenic mice harboring the int-2/Fgf-3 protooncogene under transcriptional control of mouse mammary tumor virus (MMTV) promoter/enhancer exhibit a dramatic, benign hyperplasia gland. In one int-2 transgenic line (TG.NX), this growth disturbance is evoked by pregnancy and regresses after parturition. Regression hyperplastic epithelium less complete successive pregnancies, and, within 10 months, most TG.NX stochastically develop carcinomas that are transplantable in virgin, syngeneic mice. To identify genes cooperate with cell transformation, we infected MMTV. cohort 14 animals, tumors represented clonal or oligoclonal outgrowths to five proviral MMTV integrants. Eight 35 (23%) MMTV+ exhibited insertion at Wnt-1 locus. No provirus was detected int-2, int-3, Wnt-3 loci. By Southern analysis, two had insertions same genomic location, which mapped chromosome 15. Cloning int locus identified an additional member Wnt gene family. The predicted 389-amino acid protein closely related zebrafish Wnt-10a (58% amino identity over 362 residues) based on homology designated Wnt-10b. This newly discovered family expressed embryo gland virgin but not pregnant represents candidate collaborating oncogene epithelium.