Infection of epithelial-derived cells by adenovirus vectors has myriad effects on cellular behavior and function. Some are relevant to the desired effect of the encoded transgene and therapeutic goals of gene therapy approach. The current experiments describe the induction of COX-2 protein and PGE-2 production by non-small cell lung cancer (NSCLC) cells following infection with a first generation (ΔE1, ΔE3) Ad vector. COX-2 overexpression by malignant cells has been shown to enhance cellular invasion, induce angiogenesis, regulate anti-apoptotic cellular defenses and augment immunologic resistance through production of PGE-2. Data show ΔE1, ΔE3, Ad5 vector infection induces dose-dependent increases in PGE-2 production by NSCLC cell lines. Data with UV/psoralen inactivated vectors and control vectors show this effect is dependent on Ad vector gene expression, but independent of the transgene expressed. Selective blockade of ERK with PD98029 abrogated induction of PGE-2 by Ad vectors. Consistent with these data, detectable increases in COX-2 protein were seen at 48 h after infection by Western blot that were paralleled by increases in the phosphorylation of ERK-1/2. UV/psoralen-inactivated vector did not induce COX-2 protein or ERK phosphorylation at 48 h. Further, an inhibitor of NF-kappa B (NFκB) translocation to the nucleus, SN50, had no effect on PGE-2 levels. In contrast, Ad vector infection did induce NFκB activity measured by NFκB-luciferase reporter plasmid, transfected into a NSCLC cell line. Collectively the data indicate ΔE1, ΔE3, Ad5 vector infection leads to ERK phosphorylation with parallel increases in COX-2 protein and PGE-2 production. These effects appear unrelated to NFκB and are dependent on gene expression by the vector. This information may need to be considered when defining targets for cancer gene therapy and/or the choice of viral vector.
|Number of pages||4|
|State||Published - 2002|
Bibliographical noteFunding Information:
These studies were supported by the Veterans Administration Career Development Award project No. 596-416905007-0001 and from a generous donation from the McDowell Foundation, Papa Johns/Valvano fund for cancer research.
- Non-small cell lung cancer (NSCLC)
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology