BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett’s Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2Report as inadecuate




BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett’s Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2 - Download this document for free, or read online. Document in PDF available to download.

Background

Bone morphogenetic protein 4 BMP4 signaling is involved in the development of Barrett’s esophagus BE, a precursor of esophageal adenocarcinoma EAC. In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition EMT but its function in the development of EAC is currently unclear.

Aim

To investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett’s esophagus BAR-T and adenocarcinoma OE33 cell line.

Methods

Expression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT SNAIL2, CDH1, CDH2 and Vimentin was evaluated by Q-RT-PCR and Western blot analysis.

Results

Compared to squamous epithelium SQ, BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1-5-8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis.

Conclusion

Our results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1.



Author: Christine Kestens , Peter D. Siersema, G. Johan A. Offerhaus, Jantine W. P. M. van Baal

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents