A novel TARP-promoter-based adenovirus against hormone-dependent and hormone-refractory prostate cancer

被引:34
作者
Cheng, WS
Kraaij, R
Nilsson, B
van der Weel, L
de Ridder, CMA
Tötterman, TH
Essand, M [1 ]
机构
[1] Uppsala Univ, Rudbeck Lab, SE-75185 Uppsala, Sweden
[2] Erasmus Med Ctr, Dept Urol, Josephine Nefkens Inst, Sect Oncol Urol, Rotterdam, Netherlands
关键词
TARP; promoter; PPT; prostate cancer; adenovirus; gene therapy;
D O I
10.1016/j.ymthe.2004.05.022
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
TARP (T cell receptor T-chain alternate reading frame protein) is a protein that in males is uniquely expressed in prostate epithelial cells and prostate cancer cells. We have previously shown that the transcriptional activity of a chimeric sequence comprising the TARP promoter (TARPp) and the PSA enhancer (PSAe) is strictly controlled by testosterone and highly restricted to cells of prostate origin. Here we report that a chimeric sequence comprising TARPp and the PSMA enhancer (PSMAe) is highly active in testosterone-deprived prostate cancer cells, while a regulatory sequence comprising PSAe, PSMAe, and TARPp (PPT) has high prostate-specific activity both in the presence and in the absence of testosterone. Therefore, the PPT sequence may, in a gene therapy setting, be beneficial to prostate cancer patients that have been treated with androgen withdrawal. A recombinant adenovirus vector with the PPT sequence, shielded from interfering adenoviral sequences by the mouse H19 insulator, yields high and prostate-specific transgene expression both in cell cultures and when prostate cancer, PC-346C, tumors were grown orthotopically in nude mice. Intravenous virus administration reveals both higher activity and higher selectivity for the insulator-shielded PPT sequence than for the immediate-early CMV promoter. Therefore, we believe that an adenovirus with therapeutic gene expression controlled by an insulator-shielded PPT sequence is a promising candidate for gene therapy of prostate cancer.
引用
收藏
页码:355 / 364
页数:10
相关论文
共 34 条
[11]   THE ADENOVIRUS TYPE-5 E1A TRANSCRIPTIONAL CONTROL REGION CONTAINS A DUPLICATED ENHANCER ELEMENT [J].
HEARING, P ;
SHENK, T .
CELL, 1983, 33 (03) :695-703
[12]  
Imler JL, 1996, GENE THER, V3, P49
[13]   Validation of transrectal ultrasonographic volumetry for orthotopic prostate tumours in mice [J].
Kraaij, R ;
van Weerden, WM ;
de Ridder, CMA ;
Gussenhoven, EJ ;
Honkoop, J ;
Nasu, Y ;
Bangma, CH .
LABORATORY ANIMALS, 2002, 36 (02) :165-172
[14]  
Latham JPF, 2000, CANCER RES, V60, P334
[15]   Novel prostate-specific promoter derived from PSA and PSMA enhancers [J].
Lee, SJ ;
Kim, HS ;
Yu, R ;
Lee, KR ;
Gardner, TA ;
Jung, CY ;
Jeng, MH ;
Yeung, F ;
Cheng, L ;
Kao, CH .
MOLECULAR THERAPY, 2002, 6 (03) :415-421
[16]   Transcription-targeted gene therapy for androgen-independent prostate cancer [J].
Martiniello-Wilks, R ;
Tsatralis, T ;
Russell, P ;
Brookes, DE ;
Zandvliet, D ;
Lockett, LJ ;
Both, GW ;
Molloy, PL ;
Russell, PJ .
CANCER GENE THERAPY, 2002, 9 (05) :443-452
[17]   Mechanisms of disease: Prostate cancer [J].
Nelson, WG ;
De Marzo, AM ;
Isaacs, WB .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (04) :366-381
[18]  
Rembrink K, 1997, PROSTATE, V31, P168
[19]  
ROMIJN JC, 1995, UROL RES, V23, P265
[20]   Creation of a new transgene cloning site near the right ITR of Ad5 results in reduced enhancer interference with tissue-specific and regulatable promoters [J].
Rubinchik, S ;
Lowe, S ;
Jia, Z ;
Norris, J ;
Dong, J .
GENE THERAPY, 2001, 8 (03) :247-253