| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 90 === Papillary thyroid carcinomas (PTC) is the most common follicular cell-derived thyroid cancer which is often caused by somatical rearrangement of ret gene that results in a constitutive activation of rearranged RET. Rearrangement induced transformation (RET) is a receptor tyrosine kinase involved in the development of kidney and enteric nervous system and associated with several neoplasia. Whether RET expression in PTC is elevated is not certain yet. We collected 27 cases of PTCs and 8 cases of normal thyroid. To delineate signal pathways in formation of PTC, we analyzed expression and phosphorylation of several signal proteins in downstream of RET, such as Akt and JNK, Erk1/2, and p85. We observed that levels of Akt and JNK were significantly higher in PTC than in normal thyroid tissue. However, the phosphorylation/expression ratio of Akt and JNK were not different between normal thyroid tissue and PTC. In contrast, the phosphorylation/expression ratio of Erk1/2 was markedly lower in PTC than normal thyroid tissue. Therefore, abnormally high expression of Akt and JNK in PTCs might be associated with the pathogenesis of PTC. Furthermore, there was an inverse correlation between Akt levels and phospho-Erk1/2, indicating that overexpression and activation of Akt may inhibit phosphorylation of Erk1/2 in PTC.
To clarify the regulating mechanisms involved in higher expression of Akt and JNK in PTCs, mRNA of Akt and JNK was assessed by RT-PCR. The results showed that Akt and JNK isoforms between normal thyroid tissue and PTC were not different. The up-regulation of Akt and JNK in PTC might be regulated at post-transcriptional level. We also analyzed the expression of wild-type RET in PTC and normal thyroid by RT-PCR. Wild-type RET mRNA seemed to be augmented in PTC, suggesting that the expression of wild-type RET mRNA might be important in pathogenesis of PTC.
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