title: Pyrrole-imidazole polyamide targeted to break fusion sites in TMPRSS2 and ERG gene fusion represses prostate tumor growth.
abstract: Aberrant overexpression of ERG induced by the TMPRSS2-ERG gene fusion is likely involved in the development of prostate cancer. Synthetic pyrrole-imidazole (PI) polyamides recognize and attach to the minor groove of DNA with high affinity and specificity. In the present study, we designed a PI polyamide targeting TMPRSS2-ERG translocation breakpoints and assessed its effect on human prostate cancer cells. Our study identified that this PI polyamide repressed the cell and tumor growth of androgen-sensitive LNCaP prostate cancer cells. Targeting of these breakpoint sequences by PI polyamides could be a novel approach for the treatment of prostate cancer.
authors.affiliation: Department of Urology, Nihon University School of Medicine, Tokyo, Japan; Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Obinata
authors.forename: Akiko
authors.initials: A
authors.lastname: Ito
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takayama
authors.forename: Daisaku
authors.initials: D
authors.lastname: Ashikari
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Murata
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.forename: Satoru
authors.initials: S
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050939:Gene Fusion; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009757:Nylons / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D012697:Serine Endopeptidases; C421305:TMPRSS2 protein, human
keywords: Androgen receptor; TMPRSS2-ERG; fusion gene; prostate cancer; pyrrole-imidazole polyamide
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