Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E-cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma: immunohistochemical study.
Accumulation of beta-catenin in cytoplasm occurs frequently during the pathogenesis of esophageal squamous cell carcinoma (ESCC). The mechanism leading to this alteration, however, is largely unknown. In the present study, immunohistochemistry was performed for beta-catenin, E-cadherin and Ser473 phosphorylated Akt (P-Akt) in 44 tissue samples of ESCC and corresponding normal esophageal epithelium. Exon 3 of the beta-catenin gene was analyzed by using single-strand conformation polymorphism and direct sequencing. In addition to the reduced expression of E-cadherin and membranous beta-catenin observed in 65.9% and 68% of ESCC tested, respectively, cytoplasmic accumulation of beta-catenin was also detected in 68% (30/44) cases. However, only two cases were found to have the same beta-catenin gene mutation. The data showed that cytoplasmic accumulation of beta-catenin was significantly associated with reduced expression of E-cadherin (P < 0.05) and that of membranous beta-catenin (P < 0.05). Furthermore, cytoplasmic beta-catenin was correlated significantly with lymph node metastasis (P < 0.05). In contrast, although strong staining of P-Akt occurred in 14 of 44 cases (32%), there was no significant correlation between the positive staining of P-Akt and cytoplasmic beta-catenin. Taken together these results suggest that the lost membranous beta-catenin might translocate to cytoplasm depending on reduced expression of E-cadherin, while Akt seems unlikely to play a role in this process.
Zhang
Guo
G
Laboratory of Cell and Molecular Biology, Cancer Institute and Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Zhou
Xiaobo
X
Xue
Liyan
L
Quan
Lanping
L
Wang
Yihua
Y
Zhou
Cuiqi
C
Lu
Ning
N
Wang
Quanhong
Q
Zhu
Hongxia
H
Xu
Ningzhi
N
D000328:Adult; D000368:Aged; D015820:Cadherins / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt