Enhanced adenoviral transduction efficiency in HER-2/neu-overexpressing human breast cancer cells not induced by an integrin pathway

Adenoviruses are currently widely used as vectors in gene therapy. The step s involved in adenoviral infection have been investigated, but the factors regulating viral entry to the cell have not been clearly identified. We obs erved a high adenoviral infection rate in HER-2/neu-overexpressing breast c ancer cells in vitro (435.eb1 and MCF-7/H18) and in vivo (435.eb1). We used emodin, a tyrosine kinase inhibitor that suppresses autophosphorylation an d transphosphorylation activities of the HER-2/neu tyrosine kinase, to test the role of HER-2/neu in adenoviral transduction. Emodin treatment resulte d in a marked decrease in the transduction efficiency of HER-2/neu-overexpr essing cells but not in the parental cells. Because previous studies have s hown that epidermal growth factor and tumor growth factor-alpha increase th e expression level of integrin. Because integrin alpha v is known as a prom otor of viral internalization, penetration, or both, we investigated whethe r the observed increased transduction rate in HER-2/neu transfectants was m ediated 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 de tected in HER-2/neu overexpressing cells by immunoblot analysis was similar to the level of integrin alpha v found in its parental cells. These result s suggest that HER-2/neu expression may have a significant role in the vira l transduction efficiency through an integrin alpha v independent pathway.