Homebox Genes in Normal, Preneoplastic, and Neoplastic Mammary Glands

摘要

The overall aim of this project is to improve our understanding of geneticfactors regulating the development, differentiation, function, and neoplastic progression of the breast. In 1997 we investigated the first clearly identified mammary phenotype in homeobox genes, an engineered mutation in mouse Hoxd-10 that causes a deficiency in milk production. We report that Hoxd-10 is strongly expressed in the mammary epithelium in a stage-dependent manner, with highest levels found in late pregnancy and lactation. Analysis of the phenotype is in progress, but at present it appears that the defect lies in functional differentiation. A second area of reported research is investigation of the hedgehog signaling pathway, a potential upstream regulator of Hoxd-10, other homeobox genes, and a variety of mammary-active genes. We report data showing strong expression of members of the mammalian hedgehog pathway, several of which are known oncogenes. Experiments are in progress using engineered mutations, as well as investigations of the biological activity of the hedgehog protein itself in the mammary gland.