Arising from our studies of oxysterol-induced cytotoxicity, we have derived
from the murine lymphoma cell line EL4, a daughter cell line (EL4R) which exhibits
resistance to the cytotoxic effects of oxysterols. These cells also concurrently
show cross-resistance to a number of anti-cancer drugs including vincristine,
cisplatin, etoposide, and tamoxifen. Using subtractive hybridization, we have
identified 6 genes which are specifically expressed only in EL4 cells and not
in EL4R cells. One of these genes, when stably transfected into EL4R cells,
appears to restore sensitivity to the anti-cancer drugs and oxysterols. Studies
are under way to characterize these genes and their functions.