ACTIVATION OF C-MYC GENE MEDIATES THE MITOGENIC EFFECTS OF OXALATE INLLC-PK1 CELLS, A LINE OF RENAL EPITHELIAL-CELLS

Recent studies on LLC-PK1 cells demonstrated that oxalate, a simple di carboxylic acid, acts as a mitogen for these renal epithelial cells. E xposure to oxalate initiates DNA synthesis, induces the expression of one of the early growth response genes c-myc and stimulates proliferat ion of quiescent cultures of LLC-PK1 cells. The present studies examin ed the possibility that expression of the c-myc protooncogene is oblig atory for this mitogenic response. Specifically we determined whether pretreatment with c-myc antisense oligonucleotides would block the pro liferative effects of oxalate in LLC-PK1 cells. Quiescent cultures of LLC-PK1 cells were exposed to oxalate in the presence and absence of c -myc antisense and the effects of oxalate on c-myc protein expression (Myc), DNA synthesis and cell growth were assessed. Exposure of cells to oxalate alone increased the expression of Myc within two hours. Pre treatment with c-myc antisense abolished this response. Further, pretr eatment of cells with c-myc antisense but not nonsense oligonucleotide s blocked the oxalate-induced initiation of DNA synthesis. Increases i n cell number in response to oxalate (measured after 72 hr exposure) w ere also blocked by exposure to c-myc antisense. These findings sugges t that c-myc gene expression is critical for the mitogenic effects of oxalate in LLC-PK1 cells.