Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis.
Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are well characterized, little is known about apoptotic pathways initiated within the nucleus in response to genotoxic stress. We have demonstrated previously that the nuclear, death domain-containing protein p84N5 can induce apoptosis upon transfection into cells, suggesting that it may play a role in an apoptotic pathway initiated within the nucleus. To test the possibility that N5 could be used in the gene therapy of cancer, we have generated a recombinant adenovirus engineered to express N5 and tested the effects of viral infection on the growth and tumorigenicity of tumor cells. N5 adenovirus infection significantly reduced the proliferation and tumorigenicity of breast, ovarian, and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were mediated by an induction of apoptosis as indicated by DNA fragmentation in infected cells. The results suggest that the N5 cDNA is a candidate for the gene therapy of cancer.
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
S
S
Yin
M C
MC
Hung
D W
DW
Goodrich
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016601:RNA-Binding Proteins; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C400546:THOC1 protein, human