Effects of c-Myc and TGF-Alpha on Polarized Membrane Traffic

Greater than 80% of breast cancers are derived from epithelial cells. Epithelial cells are highly polarized, with separate apical and basolateral surfaces facing the lumen and adjacent cells. In epithelial tumors the degree of malignancy is correlated with extent of loss of polarity. Mammary cells can be transformed to varying degrees by regulated expression of various oncogenes. For instance, c-Jun over-expression gives a reversible transformation and loss of polarity, while sustained c-Fos over-expression gives an irreversible, more severe transformation and loss of cell polarity. The goal of this proposal is to observe the effects of differentiation, de-differentiation, and transformation on polarized membrane traffic in mammary epithelial cells. I have been investigating the hyothesis that modulation of epithelial polarity by TGF-alpha and/or c-myc will affect the ability of mammary cells to correctly transport proteins from the TGN to the apical and basolateral PMs and during transcytosis, and will correspondingly affect expression of syntaxins.