Functionally impaired TR mutants are present in thyroid papillary cancer.

Area of Science:

• Molecular Biology
• Oncology
• Endocrinology

Background:

• Thyroid hormone receptors (TRs) are crucial transcription factors regulating cell proliferation, differentiation, and apoptosis.
• TRs are cellular homologs of the viral oncogene v-erbA.
• Cancer may involve impaired TR function due to aberrant expression or mutations.

Purpose of the Study:

• To investigate the hypothesis that TR functions are impaired in thyroid cancer tissues.
• To analyze TR expression and mutation status in human papillary thyroid carcinoma.
• To determine the functional consequences of TR mutations in tumorigenesis.

Main Methods:

• Analysis of TR beta and TR alpha mRNA and protein levels in cancerous versus healthy thyroid tissues.
• Sequencing of TR beta 1 and TR alpha 1 cDNAs from papillary thyroid cancer and control tissues.
• Assessment of trans-activation function and dominant-negative activity of mutated TRs.

Main Results:

• Significantly lower TR beta and TR alpha mRNA levels, but higher TR beta 1 and TR alpha 1 protein levels in cancer tissues.
• High prevalence of TR beta 1 (93.75%) and TR alpha 1 (62.5%) mutations in papillary thyroid cancers.
• Mutated TRs frequently lost trans-activation function and exhibited dominant-negative activity, unlike in healthy thyroids or adenomas.

Conclusions:

• Mutations in thyroid hormone receptors are common in papillary thyroid carcinoma.
• Altered TR expression and function may contribute to papillary thyroid carcinoma development.
• Mutated TRs possess impaired trans-activation and dominant-negative properties, suggesting a role in tumorigenesis.