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Tumor Induction by the c-Myc Target Genes rcl and Lactate Dehydrogenase A¹

Program in Human Genetics and Molecular Biology [B. C. L., J. E. P., C. V. D.], Departments of Medicine [B. C. L., J. E. P., S. E. C., H. S., R. Z. O., C. V. D.] and Molecular Biology and Genetics [C. V. D.], and Johns Hopkins Oncology Center [R. Z. O., C. V. D.], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

The characterization of c-Myc target genes, such as rcl and lactate dehydrogenase A (LDH-A), is critical for understanding the mechanisms of c-Myc-induced cell transformation and tumorigenesis. We have previously demonstrated that Rcl induces anchorage-independent growth in Rat1a fibroblasts and that LDH-A is required for cell transformation by c-Myc. In this study, we report that Rcl and LDH-A act synergistically to induce anchorage-independent growth. Cells expressing both Rcl and LDH-A form tumors after s.c. injection into nude mice, although neither Rcl or LDH-A overexpression alone induces tumorigenesis. The inability of Rcl and LDH-A to fully recapitulate c-Myc activity, however, indicates that other c-Myc target genes participate in tumorigenesis. In addition, cells that coexpress Rcl and vascular endothelial growth factor are more comparable with c-Myc overexpressing cells in their 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-Myc and suggest that Rcl is tumorigenic in cells that are provided with a permissive metabolic milieu.

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