E2F decoy oligodeoxynucleotides effectively inhibit growth of human tumor cells.
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.
Ahn
Jong Deok
JD
Department of Microbiology, Kyungpook National University, Daegu 701-702, Republic of Korea.
Kim
Cheorl-Ho
CH
Magae
Junji
J
Kim
Young Ho
YH
Kim
Hye Jin
HJ
Park
Kwan-Kyu
KK
Hong
SaHyun
S
Park
Keun-Gyu
KG
Lee
In Kyu
IK
Chang
Young-Chae
YC
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
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