The Myc target gene JPO1/CDCA7 is frequently overexpressed in human tumors and has limited transforming activity in vivo.
MYC is frequently overexpressed in human cancers, but the downstream events contributing to tumorigenesis remain incompletely understood. MYC encodes an oncogenic transcription factor, of which target genes presumably contribute to cellular transformation. Although Myc regulates about 15% of genes and combinations of target genes are likely required for tumorigenesis, we studied in depth the expression of the Myc target gene, JPO1/CDCA7, in human cancers and its ability to provoke tumorigenesis in transgenic mice. JPO1/CDCA7 is frequently overexpressed in human cancers, and in particular, its expression is highly elevated in chronic myelogenous leukemia blast crisis as compared with the chronic phase. In murine lymphoid tissues, ectopic human JPO1/CDCA7 expression resulted in a 2-fold increased risk of lymphoid malignancies at 1 year. The transgene, which was driven by the H2-K promoter, exhibited leaky expression in nonlymphoid tissues such as kidney. We observed a significant increased incidence of transgenic animal solid tumors, which were not seen in littermate controls. These observations suggest that JPO1/CDCA7 may contribute to Myc-mediated tumorigenesis.
Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Rebecca C
RC
Osthus
Baktiar
B
Karim
Julia E
JE
Prescott
B Douglas
BD
Smith
Michael
M
McDevitt
David L
DL
Huso
Chi V
CV
Dang
D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D016259:Genes, myc; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics
C445325:CDCA7 protein, human; C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc