title: Enhanced adenoviral transduction efficiency in HER-2/neu-overexpressing human breast cancer cells not induced by an integrin pathway.
abstract: Adenoviruses are currently widely used as vectors in gene therapy. The steps involved in adenoviral infection have been investigated, but the factors regulating viral entry to the cell have not been clearly identified. We observed a high adenoviral infection rate in HER-2/neu-overexpressing breast cancer cells in vitro (435.eb1 and MCF-7/H18) and in vivo (435.eb1). We used emodin, a tyrosine kinase inhibitor that suppresses autophosphorylation and transphosphorylation activities of the HER-2/neu tyrosine kinase, to test the role of HER-2/neu in adenoviral transduction. Emodin treatment resulted in a marked decrease in the transduction efficiency of HER-2/neu-overexpressing cells but not in the parental cells. Because previous studies have shown that epidermal growth factor and tumor growth factor-alpha increase the expression level of integrin. Because integrin alphav is known as a promotor of viral internalization, penetration, or both, we investigated whether the observed increased transduction rate in HER-2/neu transfectants was mediated through the increased expression of integrin alphav. To test this hypothesis, we examined the level of integrin alphav of in HER-2/neu overexpressing cells. We found that the level of integrin alphav expression detected in HER-2/neu overexpressing cells by immunoblot analysis was similar to the level of integrin alphav found in its parental cells. These results suggest that HER-2/neu expression may have a significant role in the viral transduction efficiency through an integrin alphav independent pathway.
authors.affiliation: Department of Surgery, Uijongbu St. Mary's Hospital, Catholic University Medical College, Uijongbu city, Kyunggi-do, 480-130, South Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: H M
authors.initials: HM
authors.lastname: Jeon
authors.forename: S A
authors.initials: SA
authors.lastname: Im
authors.forename: S N
authors.initials: SN
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae; D000257:Adenoviridae Infections / Q000209:etiology / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D004642:Emodin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D018014:Gene Transfer Techniques / Q000009:adverse effects*; D018734:Genes, erbB-2; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000009:adverse effects*; D006801:Humans; D016023:Integrins / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D016023:Integrins; D011505:Protein-Tyrosine Kinases; D004642:Emodin