Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines

Y. S. Chun, M. Saji, M. A. Zeiger, S. K. Libutti, P. Lo Gerfo, O. H. Clark

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 β- galactosidase (β-gal) is driven by the Tg gene promoter (β-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 β-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of β- 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.

Original languageEnglish (US)
Pages (from-to)1100-1105
Number of pages6
JournalSurgery
Volume124
Issue number6
DOIs
StatePublished - Jan 1 1998

Fingerprint

Thyroglobulin
Cell Line
Thyroid Neoplasms
Genes
Gene Expression
Genetic Therapy
Galactosidases
Reverse Transcriptase Polymerase Chain Reaction
Human Activities
Transfection
Thyroid Gland

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Chun, Y. S. ; Saji, M. ; Zeiger, M. A. ; Libutti, S. K. ; Lo Gerfo, P. ; Clark, O. H. / Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. In: Surgery. 1998 ; Vol. 124, No. 6. pp. 1100-1105.
@article{94a2b63ac3da46a7a7f77a2fd072ddff,
title = "Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines",
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 β- galactosidase (β-gal) is driven by the Tg gene promoter (β-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 β-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of β- 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.",
author = "Chun, {Y. S.} and M. Saji and Zeiger, {M. A.} and Libutti, {S. K.} and {Lo Gerfo}, P. and Clark, {O. H.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1067/msy.1998.92008",
language = "English (US)",
volume = "124",
pages = "1100--1105",
journal = "Surgery",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "6",

}

Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines. / Chun, Y. S.; Saji, M.; Zeiger, M. A.; Libutti, S. K.; Lo Gerfo, P.; Clark, O. H.

In: Surgery, Vol. 124, No. 6, 01.01.1998, p. 1100-1105.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Overexpression of TTF-1 and PAX-8 restores thyroglobulin gene promoter activity in ARO and WRO cell lines

AU - Chun, Y. S.

AU - Saji, M.

AU - Zeiger, M. A.

AU - Libutti, S. K.

AU - Lo Gerfo, P.

AU - Clark, O. H.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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 β- galactosidase (β-gal) is driven by the Tg gene promoter (β-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 β-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of β- 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.

AB - 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 β- galactosidase (β-gal) is driven by the Tg gene promoter (β-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 β-gal expression, whereas cotransfection with TTF-1 and PAX-8 resulted in markedly increased expression. There was no evidence of β- 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.

UR - http://www.scopus.com/inward/record.url?scp=0031758342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031758342&partnerID=8YFLogxK

U2 - 10.1067/msy.1998.92008

DO - 10.1067/msy.1998.92008

M3 - Article

C2 - 9854590

AN - SCOPUS:0031758342

VL - 124

SP - 1100

EP - 1105

JO - Surgery

JF - Surgery

SN - 0039-6060

IS - 6

ER -