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2015 ; 15
(ä): 476
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Constitutive expression of Bcl-2 induces epithelial-Mesenchymal transition in
mammary epithelial cells
#MMPMID26091803
An J
; Lv J
; Li A
; Qiao J
; Fang L
; Li Z
; Li B
; Zhao W
; Chen H
; Wang L
BMC Cancer
2015[Jun]; 15
(ä): 476
PMID26091803
show ga
BACKGROUND: Bcl-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. METHODS: In 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. RESULTS: Unexpectedly, 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.
CONCLUSION: Taken 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.
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