Reversion of tumor hepatocytes to normal hepatocytes during liver tumor regression in an oncogene-expressing transgenic zebrafish model

摘要: Tumors are frequently dependent on primary oncogenes to maintain their malignant properties (known as 'oncogene addiction'). We have previously established several inducible hepatocellular carcinoma (HCC) models in zebrafish by transgenic expression of an oncogene. These tumor strongly oncogene addicted, the induced and histologically proven liver tumors regress after suppression removal a chemical inducer. However, question whether cells eliminated or revert normal remains unanswered. In present study, we generated novel Cre/loxP line, Tg(fabp10: loxP-EGFP-stop-loxP-DsRed; TRE: CreERT2) (abbreviated CreER), order trace cell lineage during regression crossing with xmrk (activated EGFR homolog) rtTA; xmrk; krt4: EGFP) found that, HCC regression, restored contained both reverted hepatocytes (RFP+) newly differentiated (GFP+). RNA sequencing (RNA-seq) analyses RFP+ GFP+ hepatocyte populations confirmed conversion hepatocytes, most genes pathways that were deregulated stages regulation tumor-reverted hepatocytes. Thus, our lineage-tracing studies demonstrated potential for transformed This observation may provide basis development therapeutic approach targeting addicted oncogenic pathways.