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Increased stimulatory G protein in neoplastic human thyroid tissues
A E Siperstein1, R A Miller, C Landis
1Surgical Service, Veterans Administration Medical Center, San Francisco, Calif.
Surgery
|December 1, 1991
Summary
Thyroid neoplasms show elevated cyclic adenosine monophosphate (cAMP) due to increased amounts of stimulatory G protein (Gs). This study found higher Gs levels in tumors, explaining the abnormal cAMP production in thyroid cancer.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- Thyroid neoplasms exhibit elevated cyclic adenosine monophosphate (cAMP) levels.
- Thyroid-stimulating hormone receptors activate adenylate cyclase via the stimulatory G protein (Gs) to produce cAMP.
Purpose of the Study:
- To investigate if alterations in Gs protein are responsible for increased cAMP production in human thyroid neoplasms.
- To quantify the activity and amount of Gs in normal and neoplastic thyroid tissue.
Main Methods:
- Assessing TSH-stimulated cyclase activity in normal and neoplastic thyroid tissue.
- Measuring Gs activity using reconstitution studies with S49 lymphoma cells.
- Evaluating Gs protein levels via cholera toxin-mediated ADP-ribosylation and Western blotting.
Main Results:
- Neoplastic thyroid tissue showed significantly higher TSH-stimulated cyclase activity compared to normal tissue.
- Reconstitution studies indicated increased Gs activity in thyroid tumors.
- Cholera toxin assays and Western blotting revealed a 3.3-fold increase in Gs protein amount in thyroid tumors.
Conclusions:
- The biochemical defect responsible for increased cAMP production in these thyroid tumors is an elevated amount of an otherwise normal Gs protein.
- Findings highlight the role of Gs protein dysregulation in thyroid neoplasia.