Transcriptional targeting of tumors with a novel tumor-specific survivin promoter.

Abstract:

:It has been demonstrated that survivin, a novel member of the inhibitor of apoptosis (IAP) protein family, is expressed in human cancers but is undetectable in normal differentiated tissues. We employed a recombinant adenoviral vector (reAdGL3BSurvivin) in which a tumor-specific survivin promoter and a luciferase reporter gene were inserted into the E1-deleted region of adenovirus vector. Luciferase activity was measured in both multiple tumor cell lines and two primary melanoma cells infected with reAdGL3BSurvivin. Human fibroblast and mammary epithelial cell lines were used as negative controls. A reAdGL3CMV, containing the CMV promoter and luciferase gene, was used as a positive control to normalize the luciferase activity generated by the survivin promoter. Our data revealed that the survivin promoter showed high activity in both established tumor cell lines and the primary melanoma cells. In contrast, the in vivo studies indicated that the activities of survivin promoter were extremely low in the major mouse organs. The survivin promoter appears to be a promising tumor-specific promoter exhibiting a "tumor on" and "liver off" profile, and therefore, it may prove to be a good candidate for transcriptional targeting of cancer gene therapy in a wide variety of tumors.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Zhu ZB,Makhija SK,Lu B,Wang M,Kaliberova L,Liu B,Rivera AA,Nettelbeck DM,Mahasreshti PJ,Leath CA,Barker S,Yamaoto M,Li F,Alvarez RD,Curiel DT

doi

10.1038/sj.cgt.7700679

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

256-62

issue

4

eissn

0929-1903

issn

1476-5500

pii

7700679

journal_volume

11

pub_type

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