Abstract
BackgroundBcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Although much is known about the anti-apoptotic ability of Bcl-2, little information is available concerning its function in other cellular processes, such as cell differentiation.MethodsIn this study, stable cell lines from pre-malignant MCF10ATG3B mammary epithelial cells, a cell line derived from a human proliferative breast disease model, to express exogenous Bcl-2 was established. CMV promoter driven Bcl-2 expression vector or empty vector was transfected into MCF10ATG3B human mammary epithelial cells to investigate the effects of Bcl-2 on mammary epithelial cells. In addition, western blot and immunofluoresence staining were employed to testify the marker proteins of both mesenchymal and epithelial cells.ResultsUnexpectedly, a dramatic change of phenotype from epithelial cells to fibroblast-like cells was observed in Bcl-2-transfected cells. Western blot analysis and immunofluoresence staining results demonstrated that the E-cadherin and desmoplakin, markers of epithelial cells, were downregulated in the Bcl-2-transfected cells. However, N-cadherin and vimentin, markers of mesenchymal cells, were upregulated in these cells. Redistributions of cytokeratin and beta-catenin were also observed in the Bcl-2-transfected cells. Our results further showed that the Bcl-2-transfected MCF10ATG3B cells retained some epithelial markers, such as epithelial specific antigen (ESA) and epithelial membrane antigen (EMA), indicating their epithelial origin. In addition, cell migration and invasion was substantially increased in Bcl-2 transfected cells.ConclusionTaken together, our results strongly indicate that in addition to its anti-apoptotic function, Bcl-2 is also involved in the epithelial-mesenchymal transition (EMT), a fundamental mechanism in normal morphogenesis and pathogenesis of some diseases.
Highlights
B cell lymphoma/leukemia gene 2 (Bcl-2) (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis
Expression of Bcl-2 in MCF10ATG3B cells attenuates apoptosis induced by serum starvation, hydrocordisone withdrawal and tumor necrosis factor (TNF)-a treatment To investigate the effects of Bcl-2 on mammary epithelial cells, we transfected MCF10ATG3B human mammary epithelial cells either with a CMV promoter driven Bcl-2 expression vector or with an empty vector, and selected transfectants with G418 for three weeks
Our results showed that Bcl-2 was highly expressed in the Bcl-2-transfected cells compared with control cells transfected with the empty vector (Fig. 1a)
Summary
Bcl-2 (B cell lymphoma/leukemia gene-2) is the first proto-oncogene recognized to function by inhibiting programmed cell death/apoptosis. Proliferation, differentiation, and apoptosis are processes tightly regulated during development and tissue homeostasis, allowing amplification along specific lineages while preventing excess proliferation of immature cells. Dysregulation of these processes contributes to some diseases including cancer. An et al BMC Cancer (2015) 15:476 and communication with the extracellular matrix (ECM) and neighboring cell play fundamental roles in epithelial trans-differentiation into a mesenchymal phenotype which involves in some stress kinases, phosphatase2A, and phosphositide 3-kinase (PI3-kinase)/protein kinase B (AKT) [4,5,6,7], which share some similar signal transduction pathways with apoptosis regulation pathways of Bcl-2 family. Our results indicate that in addition to its antiapoptotic function, Bcl-2 may be involved in EMT during normal morphogenesis and tumorigenesis
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