Aberrant nuclear localization of beta-catenin without genetic alterations in beta-catenin or Axin genes in esophageal cancer.
BACKGROUND
beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma.


METHODS
Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression.


RESULTS
Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa.


CONCLUSIONS
A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.
Kudo
Junjo
J
Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan. dr_kudo@yahoo.co.jp
Nishiwaki
Tadashi
T
Haruki
Nobuhiro
N
Ishiguro
Hideyuki
H
Shibata
Yasuyuki
Y
Terashita
Yukio
Y
Sugiura
Hironori
H
Shinoda
Noriyuki
N
Kimura
Masahiro
M
Kuwabara
Yoshiyuki
Y
Fujii
Yoshitaka
Y
D000368:Aged; D060466:Axin Protein; D001707:Biopsy, Needle; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019913:Nuclear Localization Signals / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
D060466:Axin Protein; D004273:DNA, Neoplasm; D019913:Nuclear Localization Signals; D012097:Repressor Proteins; D051153:Wnt Proteins; D051176:beta Catenin