Dynamic telomerase gene suppression via network effects of GSK3 inhibition.

ABSTRACT:

Background

Telomerase controls telomere homeostasis and cell immortality and is a promising anti-cancer target, but few small molecule telomerase inhibitors have been developed. Reactivated transcription of the catalytic subunit hTERT in cancer cells controls telomerase expression. Better understanding of upstream pathways is critical for effective anti-telomerase therapeutics and may reveal new targets to inhibit hTERT expression.

Methodology/principal findings

In a focused promoter screen, several GSK3 inhibitors suppressed hTERT reporter activity. GSK3 inhibition using 6-bromoindirubin-3'-oxime suppressed hTERT expression, telomerase activity and telomere length in several cancer cell lines and growth and hTERT expression in ovarian cancer xenografts. Microarray analysis,

SUBMITTER: Bilsland AE 

PROVIDER: S-EPMC2714081 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature