Heparin-binding EGF-like factor augments esophageal epithelial cell proliferation, migration and inhibits TRAIL-mediated apoptosis via EGFR/MAPK signaling.
OBJECTIVE
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to stimulate the growth and migration of human keratinocytes in an autocrine or paracrine manner. Bearing in mind the preceding narratives, present study was designed to explore the role of HB-EGF on esophageal epithelial cell growth, migration and anti-apoptosis.


METHODS
HET-1A and TTn cells were treated with recombinant HB-EGF, and cell proliferation and migration were assessed by MTT and Boyden chamber assays, respectively. Anti-apoptotic effects of HB-EGF was studied by Bcl-2/Bcl-xL gene expression and utilizing a TNF-related death apoptosis inducing ligand (TRAIL).


RESULTS
Recombinant HB-EGF promotes human esophageal epithelial cell proliferation in a dose dependent manner, where 1 and 10 ng/ml doses were found to be most effective. HB-EGF induced cell migration was noted in TTn, but not in HET-1A cells. Recombinant HB-EGF induced the Bcl-2, Bcl-xL mRNA/protein expression in HET-1A and TTn cells. TRAIL induced the apoptosis in TTn, whereas it was significantly inhibited in HB-EGF treated conditions. Finally, we also revealed HB-EGF induced phosphorylation of EGFR and p38 MAPK in those cell lines, while all cellular functions were repressed by EGFR inhibitor AG1478.


CONCLUSIONS
HB-EGF promotes esophageal epithelial cell proliferation, migration and induces anti-apoptotic gene expression via EGFR/p38 MAPK phosphorylation.
Rahman
Farzana Binte
FB
Department of Internal Medicine II, Shimane University School of Medicine, Izumo, Shimane, Japan.
Ishihara
Shunji
S
Aziz
Md Monowar
MM
Mishima
Yoshiyuki
Y
Oshima
Naoki
N
Li
Yong-Yu
YY
Sanchez-Siles
Alvaro A
AA
Otani
Aya
A
Oka
Akihiko
A
Kusunoki
Ryusaku
R
Tada
Yasumasa
Y
Moriyama
Ichiro
I
Ishimura
Norihisa
N
Yuki
Takafumi
T
Kazumori
Hideaki
H
Amano
Yuji
Y
Sato
Shuichi
S
Ansary
Mesban Uddin
MU
Kinoshita
Yoshikazu
Y
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004947:Esophagus / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D005786:Gene Expression Regulation; D019254:Genes, bcl-2 / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051020:bcl-X Protein