Identification of new tumor suppressor genes based on in vivo functional inactivation of a candidate gene

As a step towards developing a new functional test for the identification of tumor suppressor genes, human wild type and mutant RE genes mere expressed in the mouse A9 fibrosarcoma cell line under the transcriptional regulation of the tetracycline repressor using two new vectors: pLNCtTA and pETI, Following passage of the transfectants in immunodeficient SCID mice, the wild type RE gene,vas deleted or functionally inactivated already after the first passage in all 20 tumors tested. In contrast, a non-functional mutant RE gene,vas maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on their functional inactivation in vivo, rather than on growth suppression. (C) 1999 Federation of European Biochemical Societies.