Abstract:
:We have designed a doxycycline-regulated form of the H1 promoter of RNA polymerase III that allows the inducible knockdown of gene expression by small interfering RNAs (siRNAs). As a proof-of-principle, we have targeted beta-catenin in colorectal cancer (CRC) cells. T-cell factor (TCF) target-gene expression is induced by accumulated beta-catenin, and is the main transforming event in these cells. We have shown previously that the disruption of beta-catenin/TCF4 activity in CRC cells by the overexpression of dominant-negative TCF induces rapid G1 arrest and differentiation. Stable integration of our inducible siRNA vector allowed the rapid production of siRNAs on doxycycline induction, followed by specific downregulation of beta-catenin. In these CRC cells, TCF reporter-gene activity was inhibited, and G1 arrest and differentiation occurred. The inhibition of two other genes using this vector system shows that it should be useful for the inducible knockdown of gene expression.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
van de Wetering M,Oving I,Muncan V,Pon Fong MT,Brantjes H,van Leenen D,Holstege FC,Brummelkamp TR,Agami R,Clevers Hdoi
10.1038/sj.embor.embor865keywords:
subject
Has Abstractpub_date
2003-06-01 00:00:00pages
609-15issue
6eissn
1469-221Xissn
1469-3178pii
embor865journal_volume
4pub_type
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