Homebox Genes in Normal, Preneoplastic, and Neoplastic Mammary Glands

摘要

The overall aim of this project is to improve our understanding of genetic factors regulating the development, differentiation, function, and neo plastid progression of the breast. In the previous year we discovered the first clearly identified mammary phenotype in homeobox genes, an engineered mutation in mouse Hoxd-10 that causes a deficiency in milk production. In 1998 we report the conclusion of this project. More important, we have carried out extensive functional and expression studies on the Hedgehog (Hh) pathway, not previously shown to be active in the breast. This pathway has been shown in several model systems to control many of the signaling pathways known to regulate mammary development, and thus has the potential to be considered a 'master regulator'. Using gene-targeted mice we have shown dramatic phenotypes associated with partial loss of receptor function and with loss of one of the transcription factors mediating Hh function. The discovery that Hh signaling is essential to mammary development has far-reaching implications for our understanding of both the normal and neoplastic breast.