Adenovirus-5 E1A suppresses differentiation of 3T3 L1 preadipocytes at lower levels than required for induction of apoptosis.

To investigate the functional relationship between the ability of the adenovirus-5 E1A oncogene product to transform with its ability to block adipocytic differentiation and induce apoptosis, we expressed E1A in the 3T3 L1 preadipocytic cell line. The results demonstrate a dramatic, quantitative reciprocal regulation of differentiation and several transformation-associated properties in response to graded levels of E1A expression, with the suppression of differentiative capacity, focus formation, and anchorage-independent proliferation requiring increasing levels of E1A. Progressively higher E1A levels were accompanied by apoptosis induction. The effect of E1A upon adipocytic differentiation as well as transformation and apoptosis required binding to the retinoblastoma-susceptibility gene product. These data reveal a dissociation between E1A signals leading to transformation, suppression of differentiation and induction of apoptosis, based on levels of expression.