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Impaired expression of a human septin family gene Bradeion inhibits the growth and tumorigenesis of colorectal cancer in vitro and in vivo.

Abstract
We have identified a novel human septin family gene Bradeion, which is specifically expressed in human colorectal cancer and malignant melanoma. In order to analyze the implications of tumor-specific gene expression, ribozymes and its derivatives were specifically designed and transfected into various colorectal adenocarcinoma cell lines for Bradeion inactivation. We constructed ribozyme expression plasmids controlled by a human tRNA(Val) promoter, and both hammerhead ribozyme and its allosteric derivative maxizyme were used for two different forms of Bradeion mRNA. The sequence-specific cleavage of Bradeion mRNA resulted in significant growth inhibition and G2 arrest in human cancer cell lines, detected by flow cytometry analysis. In addition, in vivo mice studies demonstrated marked tumor growth suppression by the Bradeion-specific ribozymes. Thus, the tumor-specific and selective marker Bradeion also provides valuable tools as a potential target for colorectal cancer therapy.
AuthorsManami Tanaka, Hiroshi Kijima, Johbu Itoh, Taroh Matsuda, Tomoo Tanaka
JournalCancer gene therapy (Cancer Gene Ther) Vol. 9 Issue 6 Pg. 483-8 (Jun 2002) ISSN: 0929-1903 [Print] England
PMID12032658 (Publication Type: Journal Article)
Chemical References
  • Cytoskeletal Proteins
  • RNA, Catalytic
  • RNA, Messenger
  • RNA, Transfer, Val
  • GTP Phosphohydrolases
  • SEPTIN4 protein, human
  • Sept4 protein, mouse
  • Septins
Topics
  • Animals
  • Colorectal Neoplasms (genetics, metabolism)
  • Cytoskeletal Proteins
  • Female
  • Flow Cytometry
  • GTP Phosphohydrolases (antagonists & inhibitors, genetics)
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Models, Genetic
  • Neoplasm Transplantation
  • Plasmids (metabolism)
  • Promoter Regions, Genetic
  • RNA, Catalytic (metabolism)
  • RNA, Messenger (metabolism)
  • RNA, Transfer, Val (metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • Septins
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured

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