Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma.
Constitutive activation of the Wnt signaling pathway as a result of genetic alterations of APC, AXIN1, and CTNNB1 has been found in various human cancers, including those of the colon, liver, endometrium, ovary, prostate, and stomach. To investigate the pathogenetic significance of constitutive activation of the Wnt signaling pathway in human lung carcinogenesis, CTNNB1 alterations in exon 3, a region known to represent a mutation hot spot, were screened in 46 lung cancer cell lines and 47 primary lung cancers. Missense mutations causing substitutions of Ser/Thr residues critical for regulation by GSK-3beta were detected in one (2%) of the cell lines, A427, and two (4%) of the surgical specimens. The three lung cancers with CTNNB1 mutations were adenocarcinomas. To explore the prevalence of constitutive activation of the Wnt signaling pathway in human lung cancer, we assessed 15 lung cancer cell lines representing major histological subtypes of lung cancers for constitutive Tcf transcriptional activity (CTTA). CTTA was observed only in the A427 adenocarcinoma cell line, but not in the remaining 14 cell lines. The data indicate that constitutive activation of the Wnt signaling pathway caused by CTNNB1 mutation is involved in the development and/or progression of a subset of lung carcinoma, preferentially in adenocarcinoma.
Sunaga
N
N
Biology Division, National Cancer Center Research Institute, Tokyo, Japan.
Kohno
T
T
Kolligs
F T
FT
Fearon
E R
ER
Saito
R
R
Yokota
J
J
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004789:Enzyme Activation / Q000235:genetics; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3