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 alpha v 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 alpha v. To test this hypothesis, we examined the level of integrin alpha v of in HER-2/neu over-expressing cells. We found that the level of integrin alpha v expression detected in HER-2/neu overexpressing cells by immunoblot analysis was similar to the level of integrin alpha v 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 alpha v independent pathway.