Role of homeobox genes in normal mammary gland development and breast tumorigenesis

The role of homeobox-containing genes in embryogenesis and organogenesis is well documented. Also, a sizeable body of evidence has accumulated and supports the fact that homeobox genes, when dysregulated, are involved in tumorigenesis. However, the precise mechanisms of homeobox gene functions are largely unknown. The mammary gland, in which most maturation occurs postnatally, provides an ideal model for studying the functions of homeobox genes in both development and tumorigenesis. The expression of many homeobox genes has been detected in both normal mammary gland and neoplastic breast tissues. In the normal mammary gland, the expression of homeobox genes is coordinately regulated by hormone and extracellular matrix (ECM) and other unknown factors in a spatial and temporal manner in both stromal and epithelial cells. Animals with misexpressed homeobox genes displayed different extents of defects in ductal proliferation, side branching, and alveoli formation, implying that homeobox genes are important for normal mammary gland development. Recent studies of homeobox genes in breast cancer cells and primary tumors indicate that they may also play a contributory or causal role in tumorigenesis by regulating the cell cycle, apoptosis, angiogenesis, and/or metastasis.