Identification of the human IAI.3B promoter element and its use in the construction of a replication-selective adenovirus for ovarian cancer therapy

Katsuyuki Hamada, Shohei Kohno, Mari Iwamoto, Hiroko Yokota, Masato Okada, Masatoshi Tagawa, Susumu Hirose, Kenshi Yamasaki, Yuji Shirakata, Koji Hashimoto, Masaharu Ito

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Little is known concerning promoters or gene therapy specific for ovarian cancer. To explore the potential use of IAI.3B isolated from ovarian cancer cells in gene therapy for ovarian cancer, we identified the promoter region of the IAI.3B gene and created a replication-selective adenovirus, AdE3-IAI.3B, driven by the promoter. Transient transfection experiments showed that the DNA segment located between -1816 and -1 bp resulted in preferential expression in ovarian cancer cells with negligible expression in squamous cell carcinoma and normal cells. The promoter activity of IAI.3B was almost the same as that of cytomegalovirus and an order of magnitude higher than those of midkine and cyclooxygenase-2 in ovarian cancer cells. AdE3-IAI.3B replicated as efficiently as the wild-type adenovirus and caused extensive cell killing in a panel of ovarian cancer cells in vitro. In contrast, squamous cell carcinoma and normal cells were not able to support AdE3-IAI.3B replication. In animal studies, AdE3-IAI.3B administered to flank and i.p. xenografts of ovarian cancer cells led to a significant therapeutic effect. These results demonstrate the usefulness of the IAI.3B promoter for generation of ovarian cancer-specific adenoviral vectors and provide a potential for the development of ovarian cancer-specific oncolytic viral therapies.

Original languageEnglish
Pages (from-to)2506-2512
Number of pages7
JournalCancer Research
Volume63
Issue number10
Publication statusPublished - 2003 May 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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