Abstract
Aberrations in the control of apoptosis represent a central feature of thyroid carcinogenesis.
However, little is known about the regulation of components of the intrinsic apoptosis
pathway in the thyroid. Using a real-time PCR approach we investigated the mRNA expression
levels of Caspase3, Caspase3 s, xIAP, Bad, and β-actin in a panel of 79 thyroid tumours.
Additionally, we assessed the activation status of Caspase3 by immunohistochemistry.
In the present study, we provide first evidence for a deregulation of the intrinsic
apoptosis pathway on the transcriptional and post-transcriptional level. Thus, malignant
thyroid tumours revealed a significant downregulation of the proapoptotic Bad. In
contrast Caspase3 s, an alternative splice variant of Caspase3 with anti-apoptotic
characteristics, was upregulated in follicular and anaplastic cancers. Moreover, papillary
thyroid tumours revealed a significant upregulation of Caspase3 mRNA. On the post-translational
level, thyroid malignancies featured an impairment in the activation of Caspase3,
since activated Caspase3 accumulated exclusively in the cytoplasm of thyroid cancer
cells, whereas follicular adenoma and normal thyroid tissues showed no cytoplasmatic
but nuclear Caspase3 distribution. Further knowledge on apoptosis-deregulation during
thyroid carcinogenesis might confer diagnostic and therapeutic benefits in the management
of thyroid cancer.
Key words
apoptosis - thyroid cancer - Caspase3 - Caspase3s - Bad - xIAP
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Correspondence
D. Fuhrer
Department of Internal Medicine
Division of Endocrinology and
Diabetology
Ph.-Rosenthal-Straße 27
04103 Leipzig
Germany
Phone: +49/341/9713 301
Fax: +49/341/9713 389
Email: fued@medizin.uni-leipzig.de