Expression of a truncated retroviral envelope gene enhances expression of normal cellular phenotypes

The envelope gene of Moloney murine leukemia virus (Mo-MLV) and its various functional domains have been studied extensively but not as much in terms of their biological effects on cell growth. In this study, we report the bi ological characterization of a truncated Mo-MLV envelope gene, LN11, which is devoid of a signal peptide. Its expression in various cell types, as com pared to the control, enabled the transduced cells to assume a more normal phenotype, which is defined by an increase in contact inhibition and factor dependence, as well as reduced tumorigenicity. LN11-transduced fibroblasts exhibited a higher degree of contact inhibition, assumed a more flattened morphology and were more adherent compared to the control. in v-abl transfo rmed hematopoietic cells, expression of LN11 resulted in slower cell growth , which was due to an enhanced dependence on exogenous growth factors. Enfo rced expression of LN11 also resulted in a slower rate of tumor development and a reduced tumor load. Thus, modification of a retroviral genome could have a significant impact on cell growth and development. This is one examp le where we need to consider the safety issue carefully when constructing r etrovirus vectors for gene therapy. Copyright (C) 2000 National Science Cou ncil, ROC and S. Karger AG, Basel.