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Iodide symporter gene expression in normal and transformed rat thyroid cells
F Trapasso1, R Iuliano, E Chiefari
1Dipartimento di Medicina Sperimentale e Clinica, Facoltà di Medicina e Chirurgian, Università di Catanzaro, 88100 Catanzaro, Italy.
Objective:
Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells.
Design And Methods:
Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability.
Results:
NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA, PC HaMSV, PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala), and PC PyMLV cell lines.
Conclusions:
Our data show that oncogene activation could play a role in affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.
Insights
Oncogene abnormalities can reduce sodium-iodide symporter (NIS) activity in thyroid cells, impacting radioiodine therapy effectiveness. Different oncogenes affect NIS expression through various mechanisms, influencing iodide uptake in tumors.
Area of Science:
- Molecular Biology
- Oncology
- Endocrinology
Background:
- Sodium-iodide symporter (NIS) activity is crucial for radioiodine detection and treatment of metastatic thyroid cancer.
- Loss of NIS activity in thyroid tissues significantly impairs radioiodine therapy efficacy.
- Understanding factors affecting NIS activity is vital for improving thyroid cancer management.
Purpose of the Study:
- To investigate the role of specific oncogene abnormalities in altering Na+/I- symporter (NIS) activity in thyroid cells.
- To determine if oncogene activation is responsible for reduced iodide uptake in thyroid cancer.
- To explore the mechanisms underlying NIS activity changes in transformed thyroid cells.
Main Methods:
- Northern blot analysis was used to assess NIS gene expression.
- Expression levels were compared between normal thyroid cells and various oncogene-transformed cell lines.
- Cell lines with differing degrees of malignancy and iodide uptake ability were utilized.
Main Results:
- Thyroid-stimulating hormone (TSH) and forskolin dose-dependently and time-dependently upregulated NIS gene expression in normal cells.
- Insulin and TPA partially inhibited NIS gene expression in normal cells.
- Oncogene-transformed cell lines exhibited reduced NIS mRNA levels, with some showing near-complete absence of expression.
Conclusions:
- Oncogene activation plays a significant role in modulating iodide uptake ability in thyroid tumoral cells.
- Diverse mechanisms are implicated in the oncogene-dependent loss of NIS activity in transformed thyroid cells.
- These findings highlight the complex interplay between oncogenes and NIS function in thyroid cancer.