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E1A products of adenoviruses reduce the expression of cellular proliferation-associated genes
H T Timmers1, D De Wit, J L Bos
1Department of Medical Biochemistry, State University of Leiden, The Netherlands.
Abstract:
Products of the adenovirus (Ad) E1A region are capable of modulating the expression of a variety of genes, both of viral and cellular origin. We have investigated the expression of two proliferation-associated genes, c-myc and JE, in various adenovirus-transformed cell lines. Rodent and human cell lines, transformed as primary cultures by the E1 region of Ad5 or of Ad12, exhibit a markedly reduced expression of both genes. Ad5 E1-transformed cells show a more pronounced reduction of c-myc RNA than Ad12 E1-transformed cells. Even the very low levels of E1A products in Ad5 E1A-immortalized cells are sufficient for this reduction. Analysis of c-myc and JE expression in cell lines, transformed by other viral or cellular oncogenes, indicated that this reduction is specific for adenoviruses. These observations show that E1A does not contribute to cellular transformation by activating the proliferation-associated genes c-myc and JE, but instead suggest an alternative mechanism of E1A-mediated transformation.
Insights
Adenovirus E1A region products reduce expression of proliferation genes c-myc and JE. This suggests E1A-mediated transformation occurs through a mechanism other than activating these key genes.
Area of Science:
- Molecular Biology
- Virology
- Oncology
Background:
- Adenovirus (Ad) E1A region products modulate gene expression.
- Proliferation-associated genes like c-myc and JE are crucial in cellular growth and transformation.
- Understanding E1A's role in gene regulation is key to deciphering viral oncogenesis.
Purpose of the Study:
- To investigate the impact of adenovirus E1A on the expression of c-myc and JE genes.
- To determine if E1A contributes to cellular transformation by activating these proliferation genes.
- To explore the specificity of E1A's effect on gene expression in adenovirus-transformed cells.
Main Methods:
- Analysis of c-myc and JE gene expression in various adenovirus-transformed rodent and human cell lines.
- Comparison of gene expression levels between cells transformed by different adenovirus serotypes (Ad5, Ad12).
- Examination of gene expression in cells transformed by other viral or cellular oncogenes.
Main Results:
- Adenovirus E1A transformation significantly reduced c-myc and JE gene expression in both rodent and human cell lines.
- Ad5 E1-transformed cells exhibited a more pronounced reduction in c-myc RNA compared to Ad12 E1-transformed cells.
- The observed reduction in c-myc and JE expression was specific to adenoviruses, not seen with other oncogenes.
Conclusions:
- Adenovirus E1A products do not activate c-myc and JE to drive cellular transformation.
- E1A-mediated transformation likely involves alternative mechanisms independent of c-myc and JE activation.
- These findings provide new insights into the molecular mechanisms of adenovirus-induced cell transformation.