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 o f tumor suppressor genes, human wild type and mutant RE genes mere expresse d in the mouse A9 fibrosarcoma cell line under the transcriptional regulati on of the tetracycline repressor using two new vectors: pLNCtTA and pETI, F ollowing passage of the transfectants in immunodeficient SCID mice, the wil d type RE gene,vas deleted or functionally inactivated already after the fi rst passage in all 20 tumors tested. In contrast, a non-functional mutant R E gene,vas maintained in all 10 tumors studied. These results suggest that tests for the identification of tumor suppressor genes may be based on thei r functional inactivation in vivo, rather than on growth suppression. (C) 1 999 Federation of European Biochemical Societies.