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Published on: August 23, 2019
Distinct regulation of intrinsic apoptosis in benign and malignant thyroid tumours
C Weidinger1, S Karger, K Krause
1Department of Internal Medicine, Division of Endocrinology and Diabetes, University of Leipzig, Leipzig, Germany.
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 beta-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.
Insights
Thyroid cancer involves apoptosis control issues. This study found key apoptosis pathway genes, Bad and Caspase3, are deregulated in thyroid tumors, impacting cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Cell Death Research
Background:
- Apoptosis control is crucial in thyroid carcinogenesis.
- Regulation of the intrinsic apoptosis pathway in thyroid tissue is poorly understood.
Purpose of the Study:
- Investigate mRNA expression of apoptosis-related genes in thyroid tumors.
- Assess the activation status of Caspase3 in thyroid malignancies.
- Identify transcriptional and post-transcriptional changes in apoptosis pathways during thyroid cancer development.
Main Methods:
- Real-time PCR to quantify mRNA levels of Caspase3, Caspase3 s, xIAP, Bad, and beta-actin in 79 thyroid tumors.
- Immunohistochemistry to evaluate Caspase3 activation status.
Main Results:
- Significant downregulation of pro-apoptotic Bad mRNA in malignant thyroid tumors.
- Upregulation of anti-apoptotic Caspase3 s splice variant in follicular and anaplastic thyroid cancers.
- Papillary thyroid tumors showed increased Caspase3 mRNA levels.
- Impaired Caspase3 activation in thyroid malignancies, with cytoplasmic accumulation of activated Caspase3.
Conclusions:
- First evidence of intrinsic apoptosis pathway deregulation at transcriptional and post-transcriptional levels in thyroid cancer.
- Altered expression of Bad and Caspase3 variants suggests their role in thyroid carcinogenesis.
- Understanding apoptosis deregulation may offer diagnostic and therapeutic advantages for thyroid cancer management.
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