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 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 Ratla 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.
Lewis
B C
BC
Program in Human Genetics and Molecular Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Prescott
J E
JE
Campbell
S E
SE
Shim
H
H
Orlowski
R Z
RZ
Dang
C V
CV
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D016259:Genes, myc; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D000080864:Lactate Dehydrogenase 5; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009699:N-Glycosyl Hydrolases; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology; D051381:Rats
D007527:Isoenzymes; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; C107935:DNPH1 protein, human; D009699:N-Glycosyl Hydrolases