<b>Results:</b> Diminished autophagy activity was observed in ATC tissues, and in vitro treatment of ATC cell lines with DLCs robustly restored hNIS and thyroglobulin expression and iodide uptake capacity.
Immunohistochemical studies showed that all ATCs lost TTF-1 and thyroglobulin expression, whereas PAX-8 expression was identified in 36% (4/11) of tumors.
The mean expression level of thyroglobulin mRNA in the ATCs and ATC cell lines was <10(2) times higher than that in the differentiated thyroid carcinomas.
Whereas after treatment with adenovirus/GCV to non-TG-producing cell lines (undifferentiated thyroid carcinoma cell lines and carcinoma cell lines from other tissues), Ad2 x TGtk and AdTGtk needed more than 100-fold concentrated GCV to reach IC(50) compared to AdCMVtk.
To develop gene therapy targeting thyroid carcinoma, the recombinant retrovirus (LNTGTK) carrying herpes simplex virus thymidine kinase (HSV-TK) gene under the control of thyroglobulin (TG) promoter was constructed and its efficacy was investigated in 3 thyroid cell lines; a differentiated normal rat thyroid cell line (FRTL5), malignant rat thyroid carcinoma cells derived from FRTL5 (FRTC) and a human anaplastic thyroid carcinoma cell line (FRO).
The main conclusions of our study are that 1) the TSH-R gene is expressed in some MTC, which supports, at molecular level, the hypothesis of the existence of mixed follicular-medullary thyroid tumors; and 2) the expression of TSH-R, Tg, and TPO in undifferentiated thyroid cancer is lost.