DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter activity via Sp1 phosphorylation

Ichiro Niina, Takeshi Uchiumi, Hiroto Izumi, Takayuki Torigoe, Tetsuro Wakasugi, Tomonori Igarashi, Naoya Miyamoto, Takamitsu Onitsuka, Masaki Shiota, Ryuichi Okayasu, Kazuo Chijiiwa, Kimitoshi Kohno

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Modification of transcription factors by anticancer agents plays an important role in both apoptotic and survival signaling. Here we report that both DNA topoisomerase I and II inhibitors such as SN-38 and etoposide, but not cisplatin, 5-fluorouracil or actinomycin D, can induce phosphorylation of the transcription factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate GC-box-dependent promoters such as the SV40 and vascular endothelial growth factor promoters. The phosphorylated form of Sp1 was detectable within 30 min of etoposide treatment and was greatly diminished by the presence of the PI3K inhibitor wortmannin and by DNA-dependent protein kinase (DNA-PK) knockdown. We also confirmed that the phosphorylated form of DNA-PK was increased by treatment with both etoposide and SN-38. Taken together, these findings demonstrate a novel genomic response to anticancer agents that induce Sp1 phosphorylation, and might contribute to tumor progression and drug resistance.

Original languageEnglish
Pages (from-to)858-863
Number of pages6
JournalCancer Science
Volume98
Issue number6
DOIs
Publication statusPublished - Jun 2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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