A new targeting approach for breast cancer gene therapy using the Heparanase promoter

被引：17

作者：

Breidenbach, Martina

Rein, Daniel T.

Schoendorf, Thomas

Khan, Kiran N.

Herrmann, Isabell

Schmidt, Torsten

Reynolds, Paul N.

Vlodavsky, Israel

Haviv, Yosef S.

Curiel, David T.

机构：

[1] Univ Alabama, Div Human Gene Therapy, Dept Med, Birmingham, AL 35294 USA

[2] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA

[3] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA

[4] Univ Alabama, Gene Therapy Ctr, Birmingham, AL 35294 USA

[5] Rhein Westfal TH Aachen, Dept Obstet & Gynecol, Aachen, Germany

[6] Univ Dusseldorf, Med Ctr, Dept Obstet & Gynecol, D-4000 Dusseldorf, Germany

[7] Univ Appl Sci, Dept Nat Sci, Rheinbach, Germany

[8] Univ Cologne, Med Ctr, Dept Obstet & Gynecol, Cologne, Germany

[9] Royal Adelaide Hosp, Adelaide, SA 5000, Australia

[10] Hadassah Hebrew Med Ctr, Dept Oncol, Jerusalem, Israel

[11] Hadassah Hebrew Med Ctr, Div Med, Jerusalem, Israel

来源：

CANCER LETTERS | 2006年 / 240卷 / 01期

关键词：

heparanase; tissue-specific promoters; transcriptional targeting; biological therapy;

D O I：

10.1016/j.canlet.2005.09.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Gene therapy with adenoviral (Ad) vectors is a promising new approach in the treatment of cancer. Strategies to restrict adenoviral-mediated transgene expression are important to avoid gene transfer into normal cells. Heparanase (HPR) is overexpressed in breast cancer but downregulated in differentiated normal tissue. Expression of the HPR gene was evaluated in breast cancer cells. Biodistribution and liver tropism was evaluated in a mouse model. HPR is highly expressed in breast cancer tissue. The HPR promoter retained its fidelity in an adenovirus context and was activated in breast cancer cells but showed low activity in normal breast cells and the murine liver. We conclude that the HPR pathway is a promising target for the development of breast cancer directed gene therapy strategies (c) 2005 Elsevier Ireland Ltd. All rights reserved.

引用

页码：114 / 122

页数：9

共 31 条

[1] The secretory leukoprotease inhibitor (SLPI) promoter for ovarian cancer gene therapy [J].

Barker, SD ;

Coolidge, CJ ;

Kanerva, A ;

Hakkarainen, T ;

Yamamoto, M ;

Liu, B ;

Rivera, AA ;

Bhoola, SM ;

Barnes, MN ;

Alvarez, RD ;

Curiel, DT ;

Hemminki, A .

JOURNAL OF GENE MEDICINE, 2003, 5 (04) :300-310

[2]

Bilbao G, 1998, ADV EXP MED BIOL, V451, P365

[3] Transduction efficacy, antitumoral effect, and toxicity of adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir therapy of hepatocellular carcinoma:: The woodchuck animal model [J].

Bilbao, R ;

Gérolami, R ;

Bralet, MP ;

Qian, C ;

Tran, PL ;

Tennant, B ;

Prieto, J ;

Bréchot, C .

CANCER GENE THERAPY, 2000, 7 (05) :657-662

[4] Heat-directed suicide gene therapy for breast cancer [J].

Brade, AM ;

Szmitko, P ;

Ngo, D ;

Liu, FF ;

Klamut, HJ .

CANCER GENE THERAPY, 2003, 10 (04) :294-301

[5]

Elkin M, 2003, CANCER RES, V63, P8821

[6]

GARVER RI, 1994, GENE THER, V1, P46

[7] A simplified system for generating recombinant adenoviruses [J].

He, TC ;

Zhou, SB ;

da Costa, LT ;

Yu, J ;

Kinzler, KW ;

Vogelstein, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (05) :2509-2514

[8] Adenoviruses in oncology - A viable option? [J].

Hemminki, A ;

Alvarez, RD .

BIODRUGS, 2002, 16 (02) :77-87

[9]

Hitt M M, 1997, Adv Pharmacol, V40, P137, DOI 10.1016/S1054-3589(08)60140-4

[10]

HUARD J, 1995, GENE THER, V2, P107

← 1 2 3 4 →