Tumor induction by the c-Myc target genes rcl and lactate dehydrogenase A

The characterization of c-Myc target genes, such as rcl and lactate dehydro genase A (LDH-II), is critical for understanding the mechanisms of c-Myc-in duced cell transformation and tumorigenesis, We have previously demonstrate d that Rcl induces anchorage-independent growth in Ratla fibroblasts and th at LDH-A is required for cell transformation by c-Myc, In this study, we re port that Rcl and LDH-A act synergistically to induce anchorage-independent growth. Cells expressing both Rcl and LDH-A form tumors after s.c, injecti on into nude mice, although neither Rcl or LDH-A overexpression alone induc es tumorigenesis. The inability of Rcl and LDH-A to fully recapitulate c-My c activity, however, indicates that other c-Myc target genes participate in tumorigenesis. In addition, cells that coexpress RcI and vascular endothel ial growth factor are more comparable with c-Myc overexpressing cells in th eir ability to form tumors in nude mice, These findings confirm Rcl and LDH -A as critical components of the cell transformation program induced by c-M yc and suggest that RcI is tumorigenic in cells that are provided with a pe rmissive metabolic milieu.