Nuclear translocations of beta-catenin and TCF4 in gastric cancers correlate with lymph node metastasis but probably not with CD44 expression.
Interaction of nuclear beta-catenin and TCF4 is the end point of canonical Wnt signaling, which is believed to trigger the transcription of multiple cancer-associated genes, including CD44. So far, the combined status of beta-catenin and TCF4 and its relevance for lymph node metastasis and CD44 expression have not been well studied in gastric cancers (GCs). To address these issues, we examined 31 GCs, 17 premalignant tissues, 10 noncancerous gastric mucosae, 17 regional lymph node metastases, and 4 human GC cell lines (MGC803, MGC823, AGS, and HGC-27) using immunohistochemical and immunofluorescence staining, reverse transcriptase polymerase chain reaction, and Western blot analysis. Frequent TCF4 up-regulation and nuclear translocation of beta-catenin were found in both primary and metastatic tumors. Standard CD44 was detected in all gastric tissue samples. The frequency of variant CD44 expression increased in parallel with stepwise gastrocarcinogenesis and tumor spread, but the rates of detection did not match that of nuclear beta-catenin and TCF4, especially in the premalignant and noncancerous samples. The data from the 4 cell lines were in accordance with the in vivo findings in terms of beta-catenin nuclear translocation, TCF4 activation, and CD44 expression. Our results suggest an established Wnt signaling pathway in most GCs, a close correlation of beta-catenin/TCF4-mediated signaling with tumor dissemination, and the unlikelihood of a direct effect of activated Wnt signaling on CD44 expression. The influence of beta-catenin-TCF4 interaction on alternative CD44 splicing was not established. These 3 alterations may be regarded as unfavorable features of GC.
Chen
Xiao-Yan
XY
Cancer Institute and Liaoning Laboratory of Cancer Genomics, College of Basic Medical Sciences, Dalian Medical University, Dalian 116027, PR China.
Wang
Zhi-Chuang
ZC
Li
Hong
H
Cheng
Xiao-Xin
XX
Sun
Yuan
Y
Wang
Xiao-Wei
XW
Wu
Mo-Li
ML
Liu
Jia
J
D021581:Active Transport, Cell Nucleus; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D005756:Gastritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051820:TCF Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin