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Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and
Paola Luciani1, Lisa Buci, Barbara Conforti
1Endocrine Unit, Departm,ent of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Objective:
Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported. The expression of the NIS gene is up-regulated by TSH through the cAMP pathway and the characterization of the promoter region of the rat NIS gene revealed the existence of a degenerate cAMP response element (CRE) sequence. The cAMP-dependent transcription factor cAMP response element-binding protein (CREB) binds to CRE acting, upon phosphorylation, as a transcriptional activator. In this study we evaluated the expression of CREB and NIS gene in thyroid non-functioning adenomas (n=18) and carcinomas (n=20), as well as in the corresponding normal tissue.
Methods:
The levels of CREB and NIS mRNA were determined by quantitative real-time RT-PCR, whereas CREB protein (total and phosphorylated) was analyzed by Western blot.
Results:
The levels of CREB mRNA in thyroid carcinomas, but not in adenomas, were significantly lower than in the corresponding normal tissue (4.63+/-0.89 vs 9.51+/-2.01 pg/microg total RNA, means+/-s.e., P=0.025). CREB protein levels, which were determined in a subset of samples, were in quite good agreement with mRNA data. NIS mRNA levels did not differ in adenomas or carcinomas, compared with the corresponding normal tissue and no significant relationship with the levels of CREB mRNA was observed.
Conclusions:
Our results have indicated for the first time that reduced levels of CREB expression are a feature of thyroid carcinomas, and confirm that different factors are likely to modulate NIS expression.
Insights
Reduced expression of cAMP response element-binding protein (CREB) is a key feature in thyroid carcinomas. This study investigated CREB and sodium/iodide symporter (NIS) gene expression in thyroid tumors, finding lower CREB mRNA in carcinomas but not adenomas.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Sodium/iodide symporter (NIS) expression is crucial for thyroid function and is regulated by thyroid-stimulating hormone (TSH) via the cAMP pathway.
- The cAMP response element-binding protein (CREB) is a transcription factor that binds to cAMP response elements (CRE) and activates gene expression upon phosphorylation.
- Previous studies suggest reduced NIS expression or targeting in thyroid tumors.
Purpose of the Study:
- To evaluate the expression of CREB and NIS genes in thyroid non-functioning adenomas and carcinomas compared to normal thyroid tissue.
- To investigate the relationship between CREB expression and NIS gene expression in these thyroid tissues.
Main Methods:
- Quantitative real-time RT-PCR was used to determine messenger RNA (mRNA) levels of CREB and NIS.
- Western blot analysis was employed to assess total and phosphorylated CREB protein levels.
- The study included 18 non-functioning adenomas and 20 carcinomas, with paired normal tissue samples.
Main Results:
- CREB mRNA levels were significantly lower in thyroid carcinomas compared to normal tissue (P=0.025), but not in adenomas.
- CREB protein levels corroborated the mRNA findings.
- No significant differences in NIS mRNA levels were observed between tumors and normal tissue, nor was a relationship found between CREB and NIS mRNA levels.
Conclusions:
- Reduced CREB expression is a characteristic finding in thyroid carcinomas.
- These findings suggest that factors other than CREB likely regulate NIS expression in thyroid tumors.
- The study highlights a potential role for CREB in thyroid carcinogenesis.