The Expression of Oncoproteins in Transitional Cell Carcinoma: Its Correlation with Pathological Behavior, Cell Cycle and Drug Resistance

Abstract

Objective: To investigate the relationship of oncoproteins with histological grade, tumor stage, cell cycle and multidrug resistance (MDR) in bladder cancer. Methods: The expression of various oncoproteins (p21, EGFR1, erbB-2, c-jun, c-myc, bcl-2, Bax) and suppressor gene products (WT-1, RB gene, p53) was studied in normal urothelium, transitional cell carcinoma (TCC) cell lines and their MDR sublines by using specific antibodies and an indirect immunofluorescence flow-cytometric method. Results: The total increased rate of measured oncoproteins in TCC cell lines was 62.7%. There was no difference in the expression rate of oncoproteins between low-grade/stage TCC cell lines and high-grade/stage TCC cell lines. All of these TCC cell lines have aneuploidy and increased proliferative activity in the cell cycle, but a correlation with oncoprotein expression was not seen. They had a low expression rate of c-myc, Bax and RB gene when compared to normal urothelium. On the contrary, the expressions of p21, EGFR1, erbB-2, bcl-2, WT-1 and p53 oncoproteins were significantly higher than in normal urothelium (p < 0.05). A long-term cultured MDR subline of TCC8702 (TCC8702/ADR1000) demonstrated a generally decreasing expression of oncoproteins in addition to p53. Conclusions: The p21, EGFR1, erbB-2, bcl-2, WT-1 and p53 oncoproteins were increased in TCC cells compared to normal urothelium. Oncoprotein expression is related to tumorigenesis of TCC cells, but no correlation was seen between the incidence and tumor differentiation and cell cycle. These oncoproteins decreased gradually in the process of generation of MDR in addition to p53. It indicates that the p53 oncogene is closely related to the acquired MDR of TCC cells.