ERBA - TUMOR-SUPPRESSOR TURNED ONCOGENE

Cancer has been commonly linked to aberrant proliferation and a failur e of the transformed cells to differentiate. Activated proto-oncogenes are thought to provide continuous proliferation signals that enhance the growth of these cells. Conversely, cellular transformation may als o be achieved by the inactivation of genes whose normal function is to constrain cell growth by either suppressing proliferation or inducing differentiation. Such an inactivation could result from dominant-nega tive mutations, leading to the expression of abnormal proteins that in hibit the function of their normal counterparts. A prototype example i s the v-erbA oncogene of the avian erythroblastosis virus (AEV), which antagonizes the transcriptional regulatory function of the chicken c- ErbA/thyroid hormone receptors (c-ErbA/TR) and the structurally relate d retinoic acid receptors (RARs). The result of this inhibition is a l oss of hormone responsiveness and hormone-induced differentiation. Her e we have a parallel to the tumor suppressor gene where it is also a l oss of function that induces the transformation process. In this way, the normal, hormone-activated c-ErbA/TRs and RARs act as growth suppre ssors because the resulting differentiated cells irreversibly lose pro liferative potential. In this article, the properties of v-ErbA will b e discussed in the context of c-ErbA/thyroid hormone and retinoic acid receptor function.