Expression of cAMP-responsive element binding protein and inducible cAMP early repressor in hyperfunctioning thyroid adenomas

Autor: M. Tonacchera, Luca Chiovato, Silvana Baglioni-Peri, Mario Serio, P Agretti, Barbara Conforti, Alessandro Peri, Paola Luciani, Lisa Buci, Federica Cioppi, G Biliotti, Paolo Vitti
Rok vydání: 2002
Předmět:
CAMP Responsive Element Binding Protein
Adenoma
Adult
Male
endocrine system
Receptor Status
medicine.medical_specialty
Thyroid Hormones
Endocrinology
Diabetes and Metabolism
Blotting
Western
CREB
Cyclic AMP Response Element Modulator
Endocrinology
Internal medicine
Gene expression
medicine
Cyclic AMP
Humans
RNA
Messenger
Thyroid Neoplasms
Phosphorylation
Transcription factor
Aged
Activating Transcription Factor 1
biology
Reverse Transcriptase Polymerase Chain Reaction
Thyroid
Receptors
Thyrotropin
General Medicine
Sequence Analysis
DNA
Middle Aged
medicine.disease
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Repressor Proteins
medicine.anatomical_structure
Luminescent Measurements
Mutation
Cancer research
biology.protein
cAMP-dependent pathway
Female
Signal Transduction
Transcription Factors
Zdroj: European journal of endocrinology. 146(6)
ISSN: 0804-4643
Popis: OBJECTIVE: The pathogenesis of thyroid hyperfunctioning adenomas is still only partially understood and controversy exists about the frequency of gain-of-function mutations of the TSH receptor or G(s)alpha gene, which activate the cAMP pathway. The nuclear transcription factors cAMP-responsive element binding protein (CREB) and inducible cAMP early repressor (ICER) are among the final targets of this signalling cascade. DESIGN: In our study we focused on the expression of CREB and ICER genes in the nodular as well as in the extranodular tissue of hyperfunctioning tumours of the thyroid. METHODS: RT-PCR and Western blot analysis were performed in a series of 14 patients. The presence of an activating mutation of the TSH receptor or of the G(s)alpha gene was ascertained by direct sequencing. RESULTS: The levels of CREB transcripts did not significantly differ in the adenomas and in the normal tissues (CREB/GAPDH, mean optical density+/-s.e.: 0.98+/-0.18 vs 0.88+/-0.27 respectively, P = not significant (N.S.)), although case-to-case variability was observed. The absence of a significant difference between the adenoma and the surrounding normal tissue was maintained after dividing the patients into two groups, according to TSH receptor status. Accordingly, no significant difference in the levels of CREB protein (total and Ser(133)-phosphorylated) was observed between the nodular and the extranodular tissue. In addition, no difference was found in the levels of ICER transcripts (ICER/GAPDH, mean optical density+/-s.e.: 0.52+/-0.11, nodule vs 0.36+/-0.11, normal thyroid, P=N.S.), independently of the TSH receptor gene status (i.e. wild-type or mutated). CONCLUSIONS: Our results support the recent hypothesis that the activation of the cAMP pathway in hyperfunctioning adenomas of the thyroid might be counteracted by opposite events and suggest that complex molecular mechanisms might take part in the pathogenesis of hyperfunctioning tumours.
Databáze: OpenAIRE
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