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Regulation of CRABP-II expression by MycN in Wilms tumor |
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| Authors: | Gupta Anu Kessler Patricia Rawwas Jawhar Williams Bryan R G |
| Affiliation: | a Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA b Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA c Pediatric Hematology and Oncology, Children's Hospitals and Clinics of Minnesota, 2525 Chicago Avenue South, Minneapolis, MN 55404, USA d Monash Institute of Medical Research, Monash University, 246 Clayton Road, Clayton, VIC 3168, Australia |
| Abstract: | Cellular retinoic acid binding protein II (CRABP-II) is overexpressed in a wide variety of cancers. Previously we have shown that CRABP-II expression levels are also elevated in neuroblastoma and Wilms tumors. To elucidate the molecular mechanisms underlying the abnormal expression of CRABP-II in Wilms tumor, we studied the expression of MycN and CRABP-II in these tumor samples. Our data revealed that CRABP-II is overexpressed in Wilms tumor compared to normal adjacent non-neoplastic tissue and its levels are even higher in late stage tumors. Its expression correlates with MycN expression in tumors. The tumors that do not express MycN have no CRABP-II expression. The expression of CRABP-II is also regulated by methylation and its promoter is unmethylated in tumors. Knockdown of MycN by small interfering RNA leads to downregulation of CRABP-II. Thus our results suggest that both MycN and DNA methylation are responsible for CRABP-II expression in pediatric tumors and demethylation of CRABP-II may be an early event in tumor development. |
| Keywords: | CRABP-II, cellular retinoic acid binding protein II MSP, methylation-specific PCR RA, retinoic acid siRNAs, small interfering RNAs |
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