OBJECTIVETo investigate the changes of gene expression profile during malignant transformation of rat liver oval-like cells and to analyze the significances of these changes.

METHODSMNNG initiated WB-F344 cells were exposed to H2O2 once a week (repeated 21 times) to induce their malignant transformation. The characteristics of the transformed cells were confirmed by morphology, genetics and soft agar assay. Then, gene expression profiles of the transformed cells at different time points were evaluated using rat Cancer PathwayFinder Oligo Microarray.

RESULTSThe transformed cells possessed heteroploid karyotypes with anchoring-independent growth characteristics. Transmission electron microscopy showed that the transformed cells had more cellular organelles, gap junctions and microvilli than the controls. The 21 differential expression genes were mainly involved in regulating cell proliferation, apoptosis, adhesion and motility. The expression of PTEN was gradually up-regulated and cdkn1a was gradually down-regulated in three groups of cells. Myc, fos, and casp-8 were first up-regulated in WB-5 cells and then down-regulated in WB-21 cells.

CONCLUSIONThe disorder of proliferation and apoptosis may play an important role in malignant transformation of WB cells. Cdkn1a, PTEN, myc and fos may be crucial factors involved in the process.