Cyclin D1 overexpression in thyroid tumours from a radio‐contaminated area and its correlation with Pin1 and aberrant β‐catenin expression

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Abstract
Cyclin D1 is a target molecule transcriptionally activated by aberrant β‐catenin in Wnt signalling, while prolyl isomerase Pin1 promotes cyclin D1 overexpression directly or through accumulation of β‐catenin in cancer cells. This study aimed to elucidate whether Pin1 was involved in cyclin D1 overexpression and aberrant β‐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 β‐catenin and/or decreased membrane β‐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 β‐catenin expression (p < 0.001), and between Pin1 and cytoplasmic (p < 0.001)/membrane (p = 0.002) β‐catenin expression in thyroid tumours. Mutation of the β‐catenin gene could not be detected in PTC. Western blot analysis demonstrated high levels of cyclin D1 and β‐catenin as well as Pin1 expression in a human PTC cell line possessing wild‐type β‐catenin and APC genes. This study suggests that both cyclin D1 overexpression and aberrant β‐catenin expression are of significance in thyroid tumours. Pin1 expression appears to correlate closely with the level of cyclin D1 and aberrant β‐catenin expression in thyroid tumours such as FA and PTC. Pin1 may be an important factor in regulating cyclin D1 and β‐catenin expression during thyroid carcinogenesis. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.