The levels of integrin alpha v beta 5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells.
Adenovirus mediated transfer of growth-inhibiting molecules, such as p53 shows promise as an effective method of suppressing the growth of cancer cells. As the basis for in vivo studies, we examined transfection efficiency using 15 human lung cancer cell lines that differ in their endogenous p53 status. When infected with an adenovirus expressing bacterial beta-galactosidase, the different cell lines showed different levels of beta-galactosidase activity. We found a correlation between the level of integrin alpha v beta 5, which is thought to be an adherence receptor for adenoviruses, and the expression level of the transferred gene, suggesting that gene expression is largely dependent on the infection efficiency. Growth inhibition was induced in all cell lines tested following infection with an adenovirus containing p53, regardless of the genetic status of their endogenous p53 provided a sufficient amount of p53 protein was expressed. Our results (1) confirm that the examination of the susceptibility of target cancer cells to an adenovirus is important when considering performing adenovirus-mediated gene transfer and for evaluating its therapeutic effects; and (2) suggest that the quantification of integrin alpha v beta 5 may be a good way of predicting the susceptibility of cells to adenoviral vectors.
Takayama
K
K
Research Institute for Diseases of the Chest, Kyushu University School of Medicine, Fukuoka, Japan.
Ueno
H
H
Pei
X H
XH
Nakanishi
Y
Y
Yatsunami
J
J
Hara
N
N
D000256:Adenoviridae / Q000235:genetics*; D000258:Adenovirus Infections, Human / Q000378:metabolism; D004198:Disease Susceptibility; D015870:Gene Expression; D018014:Gene Transfer Techniques; D016158:Genes, p53; D005822:Genetic Vectors; D006801:Humans; D016023:Integrins / Q000032:analysis*; D008175:Lung Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D009363:Neoplasm Proteins / Q000032:analysis*; D019030:Receptors, Vitronectin / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D016023:Integrins; D009363:Neoplasm Proteins; D019030:Receptors, Vitronectin; D016159:Tumor Suppressor Protein p53; C064660:integrin alphaVbeta5; D001616:beta-Galactosidase