TY - JOUR
T1 - Radiofrequency ablation for dysplasia in Barrett's esophagus restores β-catenin activation within esophageal progenitor cells
AU - Krishnan, K.
AU - Komanduri, S.
AU - Cluley, J.
AU - Dirisina, R.
AU - Sinh, P.
AU - Ko, Jeff Z.
AU - Li, L.
AU - Katzman, R. B.
AU - Barrett, T. A.
N1 - Funding Information:
Acknowledgments T. A. Barrett was supported by NIH, R01DK-54778 and R01DK-47073.
PY - 2012/2
Y1 - 2012/2
N2 - Background and Aims: Endoscopic therapies for Barrett's esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated β-Catenin signaling in regenerative epithelium. Methods: Biopsies were taken from squamous, non-dysplastic BE, dysplastic BE and esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically normal appearing neosquamous epithelium were taken at 3, 6, and 12 months after successful RFA. Immunohistochemistry and Western blot analysis was performed for Pβ-Catenin 552 (Akt-mediated phosphorylation of β-Catenin), Ki-67 and p53. Results: There was no difference in Pβ-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pβ-Catenin 552 in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a persistent threefold increase in Pβ-Catenin 552 in neosquamous epithelium 3 months after RFA compared to native squamous epithelium (P < 0.05) that correlated with increased Ki-67. Six months after RFA, Pβ-Catenin 552 and Ki-67 are similar to native squamous epithelium. Conclusions: Enhanced AKT-mediated β-Catenin activation is seen in BE-associated carcinogenesis. Three months after RFA, squamous epithelial growth from SPC populations exhibited increased levels of Pβ-Catenin 552. This epithelial response becomes quiescent at 6 months after RFA. These data suggest that elevated Pβ-Catenin 552 after RFA denotes a repair response in the neosquamous epithelium 3 months post-RFA.
AB - Background and Aims: Endoscopic therapies for Barrett's esophagus (BE) associated dysplasia, particularly radiofrequency ablation (RFA), are popular alternatives to surgery. The effect of such therapies on dysplastic stem/progenitor cells (SPC) is unknown. Recent studies suggest that AKT phosphorylation of β-Catenin occurs in SPCs and may be a marker of activated SPCs. We evaluate the effect of RFA in restoring AKT-mediated β-Catenin signaling in regenerative epithelium. Methods: Biopsies were taken from squamous, non-dysplastic BE, dysplastic BE and esophageal adenocarcinoma (EAC). Also, post-RFA, biopsies of endoscopically normal appearing neosquamous epithelium were taken at 3, 6, and 12 months after successful RFA. Immunohistochemistry and Western blot analysis was performed for Pβ-Catenin 552 (Akt-mediated phosphorylation of β-Catenin), Ki-67 and p53. Results: There was no difference in Pβ-Catenin552 in squamous, GERD, small bowel and non-dysplastic BE. There was a fivefold increase in Pβ-Catenin 552 in dysplasia and EAC compared to non-dysplastic BE (P < 0.05). Also, there was a persistent threefold increase in Pβ-Catenin 552 in neosquamous epithelium 3 months after RFA compared to native squamous epithelium (P < 0.05) that correlated with increased Ki-67. Six months after RFA, Pβ-Catenin 552 and Ki-67 are similar to native squamous epithelium. Conclusions: Enhanced AKT-mediated β-Catenin activation is seen in BE-associated carcinogenesis. Three months after RFA, squamous epithelial growth from SPC populations exhibited increased levels of Pβ-Catenin 552. This epithelial response becomes quiescent at 6 months after RFA. These data suggest that elevated Pβ-Catenin 552 after RFA denotes a repair response in the neosquamous epithelium 3 months post-RFA.
KW - AKT
KW - Barrett's esophagus
KW - Dysplasia
KW - Radiofrequency ablation
KW - Squamous epithelialium
KW - Stem/progenitor cell
KW - β-Catenin
UR - http://www.scopus.com/inward/record.url?scp=84863048396&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863048396&partnerID=8YFLogxK
U2 - 10.1007/s10620-011-1899-0
DO - 10.1007/s10620-011-1899-0
M3 - Article
C2 - 21948356
AN - SCOPUS:84863048396
SN - 0163-2116
VL - 57
SP - 294
EP - 302
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 2
ER -