These results demonstrate that gene Crem, frequently amplified in both post-PHx and spontaneous tumors of the Mdr2-KO mice, is expressed in hepatocyte nuclei in correlation with its genomic amplification in murine HCC tumors; human CREM is expressed in the tumor cell nuclei of the majority of evaluated HCCs, and is required for the efficient proliferation of human HCC cell lines in vitro. This evidence concerns the gene CREM and neoplasm.