Expression of apoptosis, cell proliferation, and drug resistance genes in pediatric Wilms' tumors

The expression of genes associated with apoptosis, cell proliferation and d nug resistance in tumor cells was investigated in two pediatric Wilms' tumo r patients (MCH-WT-1 and MCH-WT-3) for their association with cell cycle, d aunorubicin accumulation and clinical data. DNA content, cell cycle and dru g accumulation were analyzed immediately after surgery by flaw cytometry an d mRNA expression by reverse transcriptase-polymerase chain reaction. (RT-P CR) assay. Primary cell cultures were established from tumor specimens and tumor cells in both cases showed epithelial morphology. Although cell proli feration markers (Ki67 and PCNA) were expressed in both cases, MCH-WT-3 sho wed higher levels of mRNA expression, which corresponded with metastatic be havior of the tumor in the patient. While p53 and p21 mRNAs were expressed at low levels in MCH-WT1, MCH-WT-3 showed high levels of p21 mRNA only. The increased expression of cyclin kinase inhibitor (p21) in MCH-WT-3 compared to MCH-WT-I correlated with a higher percentage of G(0)/G(1) cell populati on in the tumor specimen. Despite the expression of multidrug resistance ma rkers (MDR1 and LRP) in MCH-WT-1, flow cytometric analysis showed tumor cel l populations with very low and high daunorubicin accumulation and with the absence of any effect for verapamil and dipyridamole on daunorubicin accum ulation of tumor cells.