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Updated: Sep 3, 2026
An Orthotopic Mouse Model of Anaplastic Thyroid Carcinoma
Published on: April 17, 2013
Alteration in the transmission of TSH-message to thyroid target in a transplantable rat thyroid tumor
Abstract:
Plasma membranes derived from a transplantable rat thyroid tumor (line 1-5G in Wollman's classification), which is unresponsive to thyrotropin (TSH) but is responsive to dibutyryl 3', 5' cAMP, have been evaluated to localize the defect. TSH binding in tumor plasma membrane is slightly lower than in normal rat thyroid membranes. No change in affinity, but simply a lower capacity was observed. The glycoprotein component of the TSH receptor exhibits similar binding and solubilization properties to the glycoprotein component derived from normal rat thyroid. Analogously to normal rat thyroid membranes, gangliosides more complex than N-acetylneuraminylgalactosylglucosyl-ceramide (GM3) are also present in tumor line 1-5G membranes. Phospholipid content of tumor line 1-5G is 50% lower than that of normal rat thyroid. At variance also with normal rat thyroid, 32P incorporation in tumor line 1-5G phospholipids such as phosphatidylserine and phosphatidylethanolamine is not modified after in vitro incubation with TSH. An even more pronounced effect by TSH on 32P incorporation into phosphatidylinositol is evident in tumor line 1-5G by comparison to normal. The 1-5G thyroid tumor membranes has a 12-fold higher basal adenylate cyclase activity than that of rat thyroid membranes. The high basal adenylate cyclase activity is associated with high ADP ribosylation activity. Both enzymes of tumor are only slightly responsive to TSH. These results suggest that the block in the transmission of TSH message to the cell machinery is localized to the regulatory domains between TSH receptor and adenylate cyclase catalytic subunit.
Insights
Thyroid tumor cells unresponsive to TSH show defects in signal transmission. The defect lies between the TSH receptor and adenylate cyclase, impacting cellular response.
Area of Science:
- Endocrinology
- Molecular Biology
- Cellular Signaling
Background:
- Thyrotropin (TSH) is crucial for thyroid function.
- Thyroid tumors can exhibit TSH unresponsiveness.
- Understanding signal transduction defects is key to thyroid cancer research.
Purpose of the Study:
- To investigate the molecular defect in a TSH-unresponsive rat thyroid tumor (1-5G).
- To localize the blockage in TSH signal transmission.
- To compare membrane properties of tumor cells with normal thyroid cells.
Main Methods:
- Plasma membrane isolation from normal and tumor rat thyroid tissue.
- Thyrotropin (TSH) binding assays.
- Analysis of phospholipid content and 32P incorporation.
- Measurement of adenylate cyclase and ADP ribosylation activity.
Main Results:
- Tumor membranes showed reduced TSH binding capacity but normal affinity.
- Phospholipid content was significantly lower in tumor membranes.
- Tumor cells exhibited elevated basal adenylate cyclase and ADP ribosylation activity.
- TSH failed to stimulate 32P incorporation into phospholipids in tumor cells, unlike normal cells.
Conclusions:
- The defect in TSH signal transmission is localized between the TSH receptor and the adenylate cyclase catalytic subunit.
- Altered phospholipid metabolism and high basal enzyme activity contribute to TSH unresponsiveness.
- This study identifies a specific molecular blockade in thyroid tumor signaling pathways.
