The tumorigenic potential of a cell can be suppressed when it is fused with a nontumorigenic cell. Our previous work implicated chromosome no. 11 of a normal human cell as carrying tumorigenicity suppressor information. We are now attempting to verify this and to regionally localize (map) this genetic information which presumably regulates the expression of other genes, such as oncogenes (c-onc), that control normal cell differentiation but which may be functioning abnormally in malignant cells. This could lead to identification of these regulatory gene products, which could have therapeutic implications. DNA probes for polymorphic chromosome segments are used as markers to identify the cell parental origin of the no. 11 chromosomes in intraspecies human cell hybrids. Preliminary results confirm the implication of the no. 11 of nontumorigenic diploid cells as carrying suppressor loci because these are consistently retained in suppressed hybrids but lost from tumorigenic segregants of such hybrids. Regional localization of such loci with hybrids that contain only segments of the no. 11 chromosome are in progress. Related to the foregoing is an attempt to determine if the level of transcription of a c-onc gene is important for the malignancy of lymphoma cells. Tumorigenic human lymphoma cells with a t(8;14)\chromosome are fused with nontumorigenic human diploid cells, as well as with B lymphocytes, and the tumorigenicity of the hybrids is tested in immunodeficient nude mice. The level of c-myc mRNA of the parental lymphoma cells is compared with that of the tumorigenically suppressed hybrids and of their tumorigenic derivatives to determine if suppression is associated with decreased transcription of c-myc. These findings are then correlated with immunoglobulin (Ig) expression and the chromosome content of the cells to determine if c-myc transcription correlates with expression of Ig genes (located very near c-myc on the t[8;14] chromosome) and if Ig expression and c-myc transcription are affected by a specific chromosome of the nontumorigenic cell.
NIH ExPorter
NIH ExPorter