ROLE OF THE H19 GENE IN SYRIAN-HAMSTER EMBRYO CELL TUMORIGENICITY

Carcinogen-induced transformation in Syrian hamster embryo (SHE) cells is a multistage process characterized by specific genetic alterations at each stage in the transformation process. Loss of H19 gene express ion is one of the earliest events observed, occurring in approximately 75% of the morphologically transformed cells and the subsequently der ived tumorigenic cells. To investigate the effect the loss of H19 expr ession has on SHE cell tumorigenicity, H19 expression was reestablishe d in a tumorigenic SHE cell lineage that lacked H19 expression. H19 re expression had little effect on cellular growth in vitro but did retar d tumor growth in nude mice. Analysis of the tumors that did develop f rom cells containing the H19 gene indicated that loss of exogenous H19 gene expression was probably due to changes in DNA methylation. These results demonstrate that alterations in H19 gene expression play an i mportant role in SHE cell tumorigenicity. (C) 1997 Wiley-Liss, Inc.