Homeobox genes in mammary gland development and neoplasia

Abstract

Both normal development and neoplastic progression involve cellular transitions from one physiological state to another. Whereas much is being discovered about signal transduction networks involved in regulating these transitions, little progress has been made in identifying the higher order genetic determinants that establish and maintain mammary cell identity and dictate cell type-specific responses to mammotropic signals. Homeobox genes are a large superfamily of genes whose members function in establishing and maintaining cell fate and cell identity throughout embryonic development. Recent genetic and expression analyses strongly suggest that homeobox genes may perform similar functions at specific developmental transition points in the mammary gland. These analyses also suggest that homeobox genes may play a contributory or causal role in breast cancer.

Figure 1

Phases of mammary gland development. Proliferative development in virgin animals is represented by the linear portion of the diagram. Cyclical development is represented by the circular portion of the diagram.

Figure 2

Tissue distribution of homeobox gene expression through mouse mammary gland development. Selected stages of mammary gland development are depicted with reference to the expression patterns of several homeobox genes as demonstrated by in situ hybridization. Expression at a given stage is shown by a bar above the stage. Bars are pattern coded to represent a unique tissue compartment or epithelial structure. Transition points affected by a given homeobox gene mutation are denoted by a hatched box above the arrow representing the transition.