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

Abstract

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.

• Authors: Alessandro Peri, Paola Luciani, Massimo Tonacchera, Patrizia Agretti, Silvana Baglioni-Peri, Lisa Buci, Barbara Conforti, Federica Cioppi, Giancarlo Biliotti, Mario Serio, Paolo Vitti, Luca Chiovato
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 146 Issue 6 Pg. 759-66 (Jun 2002) ISSN: 0804-4643 [Print] England
• PMID: 12039695 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Activating Transcription Factor 1
• DNA-Binding Proteins
• RNA, Messenger
• Receptors, Thyrotropin
• Repressor Proteins
• Thyroid Hormones
• Transcription Factors
• Cyclic AMP Response Element Modulator
• Cyclic AMP

Topics

• Activating Transcription Factor 1
• Adenoma (blood, metabolism)
• Adult
• Aged
• Blotting, Western
• Cyclic AMP (metabolism)
• Cyclic AMP Response Element Modulator
• DNA-Binding Proteins (biosynthesis, genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Luminescent Measurements
• Male
• Middle Aged
• Mutation
• Phosphorylation
• RNA, Messenger (analysis)
• Receptors, Thyrotropin (genetics)
• Repressor Proteins (biosynthesis, genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Sequence Analysis, DNA
• Signal Transduction
• Thyroid Hormones (blood)
• Thyroid Neoplasms (blood, metabolism)
• Transcription Factors (biosynthesis, genetics)