Ethylnitrosourea-induced tumorigenesis of the rat nervous system provides a model for the molecular analysis of cell-type specific carcinogenesis. In the peripheral nervous system, a specific point mutation of the neu (ErbB-2) gene is critically associated with the initiation of malignant transformation in Schwann precursor cells.
In rat brain, the RB13-6 monoclonal antibody recognizes a differentiation antigen transiently expressed by a subset of glial cells highly sensitive to ethylnitrosourea-transformation. The corresponding cell-surface antigen (gpl3RB13-6) is a glycoprotein related to the human and murine plasma cell glycoprotein PC-I. The cDNA and parts of the rat RB13-6 gene have been sequenced. In order to clarify the possible role of gp 130RB13-6 in the tumorigenic process, this project includes: (a) mapping and functional analysis of the 5 regulatory region of the RB13-6 gene; (b) mutation analysis of this gene; and (c) study of the phenotypic changes in cells expressing wild-type or mutant RB13-6 transgenes.