Over-expression of Apoptosis Inhibitor 5 (Api5) results in transformation of breast epithelail cells

Abstract

Api5 has been reported to be a metastatic oncogene in several cancers. However, till date, its role in breast cancer is poorly understood. Initially identified as an inhibitor of apoptosis, Api5 has also been found to enhance cellular proliferation. The primary aim of this study was to establish the role of Api5 in breast epithelial cell transformation. Three-dimensional (3D) culture of MCF10A cells, a model system biologically more relevant than traditional models, was used to answer this question. Over-expression of Api5 resulted in larger acinar structures with increased cellular proliferation and partial clearing of luminal space probably due to delayed apoptosis. These phenotypes were indicative of transformation and resembled early lesions in breast cancer. Apart from this, loss of apico-basal polarity and integrity of cell-cell junctions coupled with up-regulation of vimentin were some the key features that were observed, which indicated EMT-like phenotype. This observation was further supported by the formation of protrusion-like or ‘bulb-like’ structures. Inability of the cells to form acinar structures upon alteration of matrix stiffness further strengthened our claim that up-regulation of Api5 is sufficient to induce transformation in non-malignant breast epithelial cells. Collectively, this study demonstrated the possible role of Api5 in breast epithelial cell transformation, which may serve as a novel target for treatment of breast cancer.