Human mammary epithelial MCF12A cells stably transfected with oncogenic V12Ras exhibit a functional epithelial-to-mesenchymal transition, which is consistent with a metastatic phenotype. (a) Diagram of normal mammary epithelial cell with extensive cell–cell junctional complexes, apical–basal polarity, and apical secretion. (b) Diagram of mesenchymal-like cell with lack of cell–cell junctions and front to back polarity typical of a motile cell. (c) Immortalized but non-tumorigenic MCF12A cells form a duct-like structure in three-dimensional culture with polarized cells that have extensive cell–cell interactions – attributes of normal mammary epithelial cells in vivo, ×400. (d) MCF12A cells transfected with oncogenic Ras show characteristics of metastatic cells in three-dimensional culture, with loss of cell–cell interactions and gain of front–back polarity, which are hallmarks of the mesenchymal cell, ×400. BM, basement membrane; GJ, gap junction; JC, junctional complex; ME, myoepithelial cell; MFG, mammary fat globule.