title: E2F decoy oligodeoxynucleotides effectively inhibit growth of human tumor cells.
abstract: Abnormal cell proliferation, largely dependent upon deregulation of cell-cycle regulatory proteins, is an important feature of several forms of human cancer. The transcription factor, E2F, plays a critical role in the trans-activation of several genes involved in cell-cycle regulation, thereby regulating cell growth. We have demonstrated that E2F decoy oligodeoxynucleotides (ODNs) with a circular dumbbell structure (CD-E2F decoy) corresponding to E2F binding sites effectively inhibit cell proliferation of primary cultured cells. Here we found that the E2F decoy ODNs inhibited serum-induced promoter activity of E2F-dependent genes in a sequence-specific manner in a RB-positive human osteosarcoma, U2OS, as well as in a RB-negative human cervical carcinoma, C33A. This E2F decoy ODN strongly inhibited gene expression of endogenous E2F1 and PCNA and proliferation of these cancer cells. Our results suggest that this decoy ODN strategy could represent a powerful investigative and potentially therapeutic strategy in the prevention and treatment of cancer.
authors.affiliation: Department of Microbiology, Kyungpook National University, Daegu 701-702, Republic of Korea.
authors.forename: Jong Deok
authors.initials: JD
authors.lastname: Ahn
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.forename: SaHyun
authors.initials: S
authors.lastname: Hong
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: In Kyu
authors.initials: IK
authors.lastname: Lee
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D001483:Base Sequence; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000187:drug effects*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009838:Oligodeoxyribonucleotides; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors