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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2016 ; 11
(5
): e0155754
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like
Phenotype in Barrett s Esophagus and Esophageal Adenocarcinoma through Induction
of SNAIL2
#MMPMID27191723
Kestens C
; Siersema PD
; Offerhaus GJ
; van Baal JW
PLoS One
2016[]; 11
(5
): e0155754
PMID27191723
show ga
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.
|*Epithelial-Mesenchymal Transition
[MESH]
|Adenocarcinoma/*metabolism/pathology
[MESH]
|Adult
[MESH]
|Aged
[MESH]
|Aged, 80 and over
[MESH]
|Barrett Esophagus/*metabolism/pathology
[MESH]
|Bone Morphogenetic Protein 4/genetics/*metabolism/pharmacology
[MESH]