Impaired expression of a human septin family gene Bradeion inhibits the growth and tumorigenesis of colorectal cancer in vitro and in vivo.
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.
Tanaka
Manami
M
Department of Collaborations, National Institute of Advanced Industrial Science and Technology, Higashi, Tsukuba Science City, Ibaraki 305-8566, Japan. tanaka-minami@aist.go.jp
Kijima
Hiroshi
H
Itoh
Johbu
J
Matsuda
Taroh
T
Tanaka
Tomoo
T
D000818:Animals; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005260:Female; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D009368:Neoplasm Transplantation; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016337:RNA, Catalytic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012366:RNA, Transfer, Val / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058112:Septins; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D003598:Cytoskeletal Proteins; D016337:RNA, Catalytic; D012333:RNA, Messenger; D012366:RNA, Transfer, Val; D020558:GTP Phosphohydrolases; C492027:SEPTIN4 protein, human; C115474:Sept4 protein, mouse; D058112:Septins