A new targeting approach for breast cancer gene therapy using the heparanase promoter.
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.
Breidenbach
Martina
M
Division of Human Gene Therapy, Department of Medicine, Gene Therapy Center, 901 19th Street South, BMR2-508, University of Alabama at Birmingham, Birmingham, AL 35294-2172, USA.
Rein
Daniel T
DT
Schöndorf
Thomas
T
Khan
Kiran N
KN
Herrmann
Isabell
I
Schmidt
Torsten
T
Reynolds
Paul N
PN
Vlodavsky
Israel
I
Haviv
Yosef S
YS
Curiel
David T
DT
D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter; D015316:Genetic Therapy; D005822:Genetic Vectors; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008156:Luciferases; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D000099175:Heparanase
D005966:Glucuronidase; D008156:Luciferases; D012333:RNA, Messenger; D000099175:Heparanase