Regulation of mammary epithelial architecture by PTEN

The PTEN tumour suppressor is a core component of the phosphoinositide 3-kinase (PI3K) signalling pathway. PTEN is mutated, deleted, or otherwise silenced in over one-third of breast cancers, with another one-third carrying other activating mutations in the core PI3K signalling pathway, most of these being activating mutations in the p110α catalytic subunit of PI3K itself. The best characterised tumour suppressor roles for PTEN are the suppression of cell growth, survival, proliferation and metabolic deregulation. However, we have found that in three-dimensional cultured mammary epithelial cells, knockdown of PTEN leads to the loss of cell polarity and tissue architecture. PTEN knockdown also causes a dramatic disruption of normal tight junction formation in adherent mammary epithelial cell cultures. Since the deregulation of cell polarity is becoming recognised as a potential driving force behind the formation of some tumours, we have been further studying the mechanisms by which PTEN controls mammary epithelial cell polarity.