Prolifération cellulaire et coopération des oncogènes v- mil et v- myc

Abstract

Retroviruses which possess the property to recombine with genetic material from the cell, have cloned and activated some oncogenes and hence are a privileged source for the study of these genes. Cellular oncogene activation can occur following two non mutually exclusive ways: (i) by over-expression of their products; (ii) by modifications of their products through mutations. Retroviruses can combine these two ways of activation leading to the over-expression of a modified product. In this paper, we present results obtained in the study of MH2, a retrovirus containing two oncogenes. We have shown that the two oncogenes of MH2 (v- mil and v- myc) cooperate in vitro to transform neuroretina cells from chicken embryos. These cells which normally do not grow in a defined medium, are induced to proliferate and become transformed upon infection by MH2. Our data enabled us to show that in MH2 v- mil was responsible for the induction of proliferation and v- myc for the transformation of the proliferating cells. Using in vitro constructs we located two regions in the protein encoded by v- mil which are important for its mitogenic property. We have also cloned the cellular counterpart of v- mil and the study of its biological activity on neuroretina cells enabled us to propose a mechanism of activation of the cellular gene by truncation of its 5′ part.