Correlation of beta-catenin and cyclin D1 expression in colon cancers.
OBJECTIVE
Beta-catenin activates transcription by TCF/LEF and has been regarded as an oncogene in a wide range of malignant tumors. Among various molecules regulated by beta-catenin/Tcf, cyclin D1 is the most likely candidate for stimulation of the oncogenic pathway. The association between beta-catenin and cyclin D1 was investigated using clinical samples from colorectal cancers.


METHODS
The expression of beta-catenin and cyclin D1 was investigated by immunohistochemical analyses of samples from 70 patients with colorectal cancers. In 28 of the fresh tumor samples, beta-catenin protein was separated into soluble and insoluble fractions and quantitatively correlated with cyclin D1 protein by Western blot analysis.


RESULTS
Compared with noncancerous epithelium, beta-catenin and cyclin D1 were overexpressed (+) in 35 (50%) and 30 cases (43%), respectively. Cyclin D1 (+) was observed in 74% (26/35) of beta-catenin (+) cases, but only in 11% (4/35) of the beta-catenin (-) cases. Thus, there was a strong association between the expression of beta-catenin and that of cyclin D1 (p < 0.001). In the Western blot analysis, the amount of cyclin D1 correlated well with beta-catenin expression in the soluble fraction (p = 0.0016), but not with beta-catenin in the insoluble fraction or with E-cadherin expression. Beta-catenin (-)/cyclin D1 (-) cases displayed less tumor invasion than the remaining cases. However, there were no significant differences in lymph node metastasis or other clinicopathological findings.


CONCLUSIONS
Our results indicate that beta-catenin overexpression in the cytoplasm may promote malignant transformation by triggering cyclin D1 expression in colorectal cancers.
Utsunomiya
T
T
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Doki
Y
Y
Takemoto
H
H
Shiozaki
H
H
Yano
M
M
Sekimoto
M
M
Tamura
S
S
Yasuda
T
T
Fujiwara
Y
Y
Monden
M
M
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D015820:Cadherins / Q000032:analysis; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003110:Colonic Neoplasms / Q000737:chemistry* / Q000473:pathology; D019938:Cyclin D1 / Q000032:analysis*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D006801:Humans; D009363:Neoplasm Proteins / Q000032:analysis*; D012189:Retrospective Studies; D015534:Trans-Activators; D051176:beta Catenin
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1