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Molecular Basis of Cancer, General Considerations: Dual Effects of Adenovirus E1A Gene as Tumor Suppressor Gene and as Oncogene

Issue: Vol.2, No.2 - January 2003

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  1. Dr Santiago Ramon y Cajal Agueras
    Clinica Puerta de Hierro, C/Scan Martin de Porres

In this article, same important points regarding human carcinogenesis are discussed. Oncogenes, tumor heterogeneity and the adenovirus E1A gene as a tumor suppressor gene and as an oncogene are also summarized.

Our previous studies dealt with the tumor variability induced by the activation of different oncogenes at the morphological and biological levels, as well as in response to anti-tumor, chemo-therapeutic and radio-therapeutic agents. Using a model of non-tumorigenic keratinocytes, we demonstrated that the adenovirus E1A gene induces a marked sensitivity to chemotherapeutic agents and gamma radiation. We also demonstrated, that in murine and human malignant tumor cell lines with multiple genetic alternations, including a mutated p53 gene or H-ras or E6 from HPVm were very sensitive to DNA-damaging agents after expression of the adenovirus E1A gene. We have studied the vivo effect of the expression on the malignant cells and after the infection with retrovirus ?E1A or with adenoviruses defective of both E1B genes, which can counteract the effects the effects of both E1B genes, which can counteract the effects of the E1A.

In summary, we have shown that: a) The constitutive expression of the E1A gene in carcinoma cells and the injection of retrovirus E1A gene in producer cells in tumors is associated with a decrease in the tumorigenicity in vivo. b) Infection by E1B-defective adenoviruses increase the cellular cytotoxic response to treatment with cisplatin and radiotherapy. c) On the basis of these results, which demonstrate the in vivo anti-tumor effect of adenovirus E1A gene and a marked sensitization to DNA-damaging anti-tumor agents, we propose that adenovirus E1A gene can be considered as a new approach in anti-tumor gene therapy.

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