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Inhibition of Angiogenesis and Induction of Apoptosis Are Involved in E1A-mediated Bystander Effect and Tumor Suppression¹

Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Adenovirus type 5 E1A has been implicated in mediation of tumor suppression. Preclinical gene therapy studies have additionally shown that complete growth suppression can be achieved by incomplete transfer of E1A into tumors, suggesting that a bystander effect may also be associated with E1A. In this study, we investigated the E1A-mediated bystander effect and the mechanisms that may be associated with it. By s.c. inoculating nude mice with a mixture of E1A transfectants and parental cells, we found that the E1A transfectants exhibited a bystander effect on inhibition of tumor growth. We further showed that E1A mediated suppression of angiogenesis and induction of apoptosis in the tumors, likely contributing to the bystander effect. In addition, coculture of E1A transfectants and parental cells in a Transwell unit led to growth retardation and apoptosis mediated by the supernatant in the parental cells, indicating that a secreted factor may also contribute to the bystander effect. Taken together, our results suggested that E1A mediates a bystander effect on tumor suppression by inhibiting angiogenesis and inducing apoptosis.

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