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Cell kinetics, DNA content and TSH receptor-adenylate cyclase system in differentiated thyroid cancer
1Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Republic of China.
Abstract:
The purpose of this study was to elucidate the changes of the TSH receptor-adenylate cyclase system in differentiated thyroid carcinomas, and their relationships with nuclear DNA content, cell kinetics and clinical stage. The results showed that the papillary carcinomas had an impaired TSH receptor-adenylate cyclase system. The production of cAMP stimulated by TSH was decreased when compared with non-cancerous tissue and high-affinity TSH receptors were reduced in number or even completely lost (nine in 24 cases). Follicular carcinomas also showed a reduction in, or even complete loss, of high-affinity TSH receptor (one in five cases). However, the responses to the stimulation of TSH, Gpp (NH)p and forskolin were not different from those in non-cancerous tissue. Papillary and follicular cancer cells showed more proliferative activity than those in non-cancerous tissue. Follicular carcinomas contained more hyperploid cells (DNA content greater than 2.5 C) than papillary carcinomas. There were no differences in cell kinetics, DNA content or the effects of Gpp (NH)p or forskolin on adenylate cyclase activity between those papillary carcinomas with high-affinity TSH receptor and those without. However, the presence of high-affinity TSH receptors had higher cAMP generation stimulated by TSH. The patients having papillary carcinomas in the absence of high-affinity TSH receptors were all in clinical stage III. These studies suggest that TSH receptors are the major sites influenced in the TSH receptor-adenylate cyclase system in papillary carcinomas. The TSH receptor-adenylate cyclase system of papillary carcinomas differs more from normal than does that of follicular carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Thyroid cancer cells, particularly papillary types, show impaired TSH receptor-adenylate cyclase systems, with reduced TSH receptors impacting cAMP production and disease staging.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- The TSH receptor-adenylate cyclase system is crucial for thyroid function.
- Alterations in this system are implicated in thyroid carcinomas.
- Understanding these changes is vital for diagnosis and treatment.
Purpose of the Study:
- To investigate alterations in the TSH receptor-adenylate cyclase system in differentiated thyroid carcinomas.
- To correlate these changes with nuclear DNA content, cell kinetics, and clinical stage.
- To differentiate the molecular behavior of papillary and follicular thyroid carcinomas.
Main Methods:
- Analysis of TSH receptor-adenylate cyclase system activity in thyroid carcinoma tissues.
- Measurement of cyclic AMP (cAMP) production stimulated by TSH, Gpp(NH)p, and forskolin.
- Assessment of nuclear DNA content and cell proliferation (kinetics).
- Correlation of molecular findings with clinical staging.
Main Results:
- Papillary thyroid carcinomas exhibited an impaired TSH receptor-adenylate cyclase system with reduced cAMP production and loss of high-affinity TSH receptors.
- Follicular carcinomas also showed reduced high-affinity TSH receptors but maintained normal responses to TSH and other stimulators.
- Cancer cells displayed higher proliferative activity; follicular carcinomas had more hyperploid cells.
- Absence of high-affinity TSH receptors in papillary carcinomas correlated with advanced clinical stage (Stage III).
Conclusions:
- TSH receptors are significantly affected in papillary thyroid carcinomas, impacting the TSH receptor-adenylate cyclase system.
- The TSH receptor-adenylate cyclase system in papillary carcinomas shows greater deviation from normal compared to follicular carcinomas.
- Loss of high-affinity TSH receptors is a key molecular alteration associated with advanced papillary thyroid cancer.