Abstract:
BACKGROUND:In anticipation of developing gene therapy against thyroid carcinoma we created an expression vector using the thyroglobulin (Tg) gene promoter. The inhibition of both Tg and thyroid-specific transcription factor (TTF-1 and PAX-8) gene expression, however, has been well documented in thyroid carcinomas. We therefore examined the effects of overexpression of TTF-1 and PAX-8 on Tg gene promoter activity in the human thyroid carcinoma cell lines, ARO (anaplastic) and WRO (follicular). METHODS:ARO, WRO, and nonthyroid cells were transfected with an expression vector in which beta-galactosidase (beta-gal) is driven by the Tg gene promoter (beta-gal). Tg, TTF-1, and PAX-8 gene expression were also examined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS:ARO and WRO exhibited decreased gene expression of Tg, TTF-1, and PAX-8. Transfection with TG--gal alone exhibited minimal beta-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of beta-gal expression with or without TTF-1 and PAX-8 in nonthyroid cells. CONCLUSIONS:Weak Tg gene promoter activity in ARO and WRO is associated with decreased expression of transcription factors TTF-1 and PAX-8 but can be restored with their overexpression. This model may serve as a template on which to further develop cell-specific gene therapy against thyroid carcinoma.
journal_name
Surgeryjournal_title
Surgeryauthors
Chun YS,Saji M,Zeiger MAdoi
10.1067/msy.1998.92008subject
Has Abstractpub_date
1998-12-01 00:00:00pages
1100-5issue
6eissn
0039-6060issn
1532-7361pii
S0039-6060(98)70056-Xjournal_volume
124pub_type
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