In the normal mammary gland, distinct Hox genes exhibit specific expression patterns and functions along its successive development phases, from prenatal stages to lactation at adulthood . Hoxc6 is expressed during mammary development and this expression declines during pregnancy while Hoxa9, Hoxb9 and Hoxd9 are required for the expansion and/or differentiation of the mammary epithelial ductal system in response to pregnancy and targetted disruption of Hoxd10, leads to a failure in alveolar expansion in late pregnancy and concomitant lactation defect . In addition to their involvement in the normal mammary gland biology, studies have shown that some Hox genes are repressed or overexpressed in mammary carcinomas and Tofacitinib supplier therefore influence cancer progression. For example, when HOXA10 is expressed in both benign and malignant breast tissue in adult women, it impacts on tumor cell phenotype by decreasing cell invasiveness and upregulating the tumor suppressor gene p53 . HOXA5 is also a positive regulator of p53 in the normal breast tissue. In human breast tumors, p53 expression can be dramatically decreased by a compromised HOXA5 function , and expression of HOXA5 in epithelial cancer cells displaying wildtype p53 led to apoptotic cell death. HOXD10 also has a tumor suppressor function. Its expression is progressively reduced in epithelial cells as malignancy increases in breast tumors and restored Hoxd10 activity inhibits tumor development in mouse xenografts and impairs migration of tumor cells . HOXA9 positively regulates BRCA1 expression and represses breast tumor growth and malignancy . While several Hox proteins act as tumor suppressors, HOXB7 is overexpressed in primary breast carcinoma and metastasis, and it stimulates tumor progression by promoting epithelial-mesenchymal transition . Hoxa1 is one of the first Hox genes to be expressed during embryonic development . Gene inactivation has demonstrated its functional importance for hindbrain segmentation, hindbrain patterning, inner and middle ear organogenesis and skull basis morphogenesis .