H19 EXPRESSION AND TUMORIGENICITY OF CHORIOCARCINOMA DERIVED CELL-LINES

Certain embryonal tumors demonstrate a loss of heterozygosity at the p arentally imprinted region of chromosome 11p15.5. It has been hypothes ized that this implicates a tumor suppressor gene at this locus. The h uman H19 gene maps to 11p15.5, is expressed in fetal tissues including the placenta and is paternally imprinted, Here we show that the abund ance of H19 transcripts in cells of two choriocarcinoma derived cell l ines (JAr and JEG-3) differs greatly. While JAr cells express high lev els of H19 RNA, the expression of H19 in JEG-3 cells is much lower tha n that of normal trophoblasts, Cells of these two cell lines were subc utaneously injected into nude mice with subsequent tumor formation, A fivefold increase in the H19 RNA level was measured in tumors derived from JEG-3 cell lines as compared to these cells before injection, How ever this increase in H19 RNA did not alter the clonogenicity in soft agar nor the growth rate of the cells derived from these tumors as com pared to the original JEG-3 cells, Nevertheless, the cells retaining t he elevated level of H19 transcripts were more tumorigenic than the or iginal cells, We propose that there is a selection of cells expressing high levels of H19 from the total JEG-3 cell population during the mi croevolution of tumor formation. These observations, together with our previous publications on H19 expression in human cancers, do not supp ort the notion of a tumor suppressor role for the H19 gene.