Targeting distinct apoptotic pathways in mammary gland involution

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Cells grow and divide to produce more cells. During growth of an embryo, certain cells have to be removed for proper function in the adult animal. An interesting example is seen in limb development. Ducks have webbed feet but human embryos also have webbed fingers and toes before they are born. The skin cells between the digits is removed by inducing them to die. This is a normal process. However, sometimes things go wrong and either too many cells, or the wrong type of cells, are made. Occasionally also, mistakes are made in copying the cell's DNA and this could cause cancer to develop. In order to eliminate this problem, and to remove normal cells that are no longer required, all cells have acquired the ability to kill themselves by activating a series of steps that result in the components of the cell being dismantled and packaged into small fragments. This cellular debris is then eaten up, or engulfed, by professional phagocytes whose job is to remove dead cells and clear away debris to prevent further damage to the surrounding tissue. This is called programmed cell death, or apoptosis. Apoptosis is very important in the lactating breast where it is needed to remove the milk producing cells when the baby is weaned and no longer needs breast feeding. We have been studying the apoptotic events that take place in breast cells and how these are controlled. We have found that the transcription factor Stat6, which binds to DNA to induce transcription of specific genes, is important for initiating apoptosis. In this project, we aim to identify genes are controlled by Stat6 and how they are involved in killing mammary cells.