Cyclin D1 overexpression in thyroid tumours from a radio-contaminated area and its correlation with Pin1 and aberrant beta-catenin expression.
Cyclin D1 is a target molecule transcriptionally activated by aberrant beta-catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of beta-catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant beta-catenin in thyroid tumourigenesis by examining 14 follicular adenomas (FAa) and 14 papillary thyroid carcinomas (PTCs). All PTCs displayed cyclin D1 overexpression and strong cytoplasmic beta-catenin and/or decreased membrane beta-catenin expression by immunohistochemistry. Overexpression of cyclin D1 mRNA was observed in 45.5% of FAs and 54.5% of PTCs by TaqMan real-time PCR. Pin1 expression was observed in PTC by immunostaining and was confirmed by reverse transcriptase-PCR. There was a strong correlation between cyclin D1 and Pin1/cytoplasmic/membrane beta-catenin expression (p < 0.001), and between Pin1 and cytoplasmic (p < 0.001)/membrane (p = 0.002) beta-catenin expression in thyroid tumours. Mutation of the beta-catenin gene could not be detected in PTC. Western blot analysis demonstrated high levels of cyclin D1 and beta-catenin as well as Pin1 expression in a human PTC cell line possessing wild-type beta-catenin and APC genes. This study suggests that both cyclin D1 overexpression and aberrant beta-catenin expression are of significance in thyroid tumours. Pin1 expression appears to correlate closely with the level of cyclin D1 and aberrant beta-catenin expression in thyroid tumours such as FA and PTC. Pin1 may be an important factor in regulating cyclin D1 and beta-catenin expression during thyroid carcinogenesis.
Nakashima
Masahiro
M
Tissue and Histopathology Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan. moemoe@net.nagasaki-u.ac.jp
Meirmanov
Serik
S
Naruke
Yuki
Y
Kondo
Hisayoshi
H
Saenko
Vladimir
V
Rogounovitch
Tatiana
T
Shimizu-Yoshida
Yuki
Y
Takamura
Noboru
N
Namba
Hiroyuki
H
Ito
Masahiro
M
Abrosimov
Aleksander
A
Lushnikov
Eugeny
E
Roumiantsev
Pavel
P
Tsyb
Anatoly
A
Yamashita
Shunichi
S
Sekine
Ichiro
I
D000328:Adult; D002471:Cell Transformation, Neoplastic; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009363:Neoplasm Proteins / Q000378:metabolism*; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018788:Radioactive Hazard Release; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000209:etiology / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D051176:beta Catenin; D019938:Cyclin D1; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase