Overexpression of Human Dickkopf-1, an Antagonist of wingless/WNT Signaling, in Human Hepatoblastomas and Wilms’ Tumors

摘要: Hepatoblastomas (HBs) represent the most frequent malignant liver tumors of childhood; yet little is known about molecular pathogenesis and alterations in expression patterns these tumors. We used a suppression subtractive hybridization approach to identify new candidate genes that may play role HB tumorigenesis. cDNA species derived from corresponding fetal were subtracted cDNAs, series interesting candidates isolated differentially expressed. One transcripts overexpressed was human Dickkopf-1 (hDkk-1) gene, which encodes secreted protein acting as potent inhibitor wingless/WNT signaling pathway. examined hDkk-1 levels 32 biopsy specimens samples, 4 cell lines, panel other normal tissues using differential PCR Northern blotting. Eighty-one percent HBs but none pediatric or showed expression. also present 5 6 Wilms’ only weakly detectable 2 20 hepatocellular carcinoma samples 1 medulloblastoma lines; absent gliomas breast cancer. The central effector molecule WNT developmental control pathway β-catenin protein. Interestingly, activating mutations gene have previously been identified 48% HBs, more than 85% show accumulation indicator for an activated overexpression Dkk-1 therefore be related uncontrolled negative feedback mechanism. represents novel marker