RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors

Andrew G. Winter, George Sourvinos, Simon J. Allison, Kerrie Tosh, Pamela H. Scott, Demetrios A. Spandidos, Robert J. White

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is overexpressed in tumors. This factor, TFIIIC2, is a histone acetyltransferase that is required for synthesis of most pol III products, including tRNA and 5S rRNA. TFIIIC2 is a complex of five polypeptides, and mRNAs encoding each of these subunits are overexpressed in human ovarian carcinomas; this may explain the elevated TFIIIC2 activity that is found consistently in the tumors. Deregulation in these cancers is unlikely to be a secondary response to rapid proliferation, because there is little or no change in TFIIIC2 mRNA levels when actively cycling cells are compared with growth-arrested cells in culture. Using purified factors, we show that raising the level of TFIIIC2 is sufficient to stimulate pol III transcription in ovarian cell extracts. The data suggest that overexpression of TFIIIC2 contributes to the abnormal abundance of pol III transcripts in ovarian tumors.

Original languageEnglish
Pages (from-to)12619-12624
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number23
DOIs
Publication statusPublished - 7 Nov 2000
Externally publishedYes

Fingerprint

RNA Polymerase III
Neoplasms
Histone Acetyltransferases
Messenger RNA
Transfer RNA
Cell Extracts
transcription factor TFIIIC
Transcription Factors
Cell Culture Techniques
Carcinoma
Peptides
Growth

Cite this

Winter, Andrew G. ; Sourvinos, George ; Allison, Simon J. ; Tosh, Kerrie ; Scott, Pamela H. ; Spandidos, Demetrios A. ; White, Robert J. / RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 23. pp. 12619-12624.
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RNA polymerase III transcription factor TFIIIC2 is overexpressed in ovarian tumors. / Winter, Andrew G.; Sourvinos, George; Allison, Simon J.; Tosh, Kerrie; Scott, Pamela H.; Spandidos, Demetrios A.; White, Robert J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 23, 07.11.2000, p. 12619-12624.

Research output: Contribution to journalArticle

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AU - Winter, Andrew G.

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AB - Most transformed cells display abnormally high levels of RNA polymerase (pol) III transcripts. Although the full significance of this is unclear, it may be fundamental because healthy cells use two key tumor suppressors to restrain pol III activity. We present the first evidence that a pol III transcription factor is overexpressed in tumors. This factor, TFIIIC2, is a histone acetyltransferase that is required for synthesis of most pol III products, including tRNA and 5S rRNA. TFIIIC2 is a complex of five polypeptides, and mRNAs encoding each of these subunits are overexpressed in human ovarian carcinomas; this may explain the elevated TFIIIC2 activity that is found consistently in the tumors. Deregulation in these cancers is unlikely to be a secondary response to rapid proliferation, because there is little or no change in TFIIIC2 mRNA levels when actively cycling cells are compared with growth-arrested cells in culture. Using purified factors, we show that raising the level of TFIIIC2 is sufficient to stimulate pol III transcription in ovarian cell extracts. The data suggest that overexpression of TFIIIC2 contributes to the abnormal abundance of pol III transcripts in ovarian tumors.

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