Changes of Oncoproteins in Drug-Resistant Cancer Cells of the Urinary Tract

各種泌尿道抗藥性腫瘤細胞癌蛋白之變化

于大雄(Dah-Shyong Yu) ； 陳宏一(Hong-I Chen) ； 張聖原(Sun-Yran Chang)

《臺灣泌尿科醫學會雜誌》 14卷1期 (2003/03) Pp. 12-16

摘要

研究目的：探討泌尿道腫瘤後天性抗藥性之產生是否與癌蛋白之改變相關。
材料與方法：利用特定抗體免疫燭光流式細胞測定分析檢測培養之腎細胞癌，膀胱癌及攝護腺癌抗藥性細胞株各種癌蛋白(ras, erbB-2, c-jun, c-myc, bcl-2, 及Bax)及抑制基因(wt-1, RB基因,及p53)之表現，並探討其間之相關性。
結果：在抗藥性腎細胞癌方面，培養早期除RB基因外所有癌基因皆升高，晚期則所有癌基因皆下降。抗藥性膀胱細也有類似表現，早期皆升高，晚期則除p53癌基因外皆下降。至於抗藥性攝護腺癌細胞在癌基因改變上則不一致，其中bcl-2, Bax, p53及WT-1基因蛋白出現增加情形。
結論：除攝護腺癌外，腎臟癌及膀胱癌細胞在產生後天抗藥性過程中，早期多種癌基因蛋白皆有增加情形。在晚期則發現RB基因蛋白於腎臟癌細胞株，p53癌基因蛋白於膀胱癌細胞株持續增加。這種現象說明了RB基因蛋白及p53癌基因蛋白分別與腎臟癌及膀胱癌之後天性抗藥性之產生有關。

關鍵字

癌基因蛋白 ； 腎臟癌 ； 膀胱癌 ； 攝護腺癌

並列摘要

OBJECTIVE: The possible relationship between oncogenetic changes and the generation of acquired multidrug resistance (MDR) in urinary tract cancers is investigated.
MATERIALS AND METHODS: The expressions of various oncoproteins (ras, erb
B-2, c-jun, c-myc, bcl-2, and Bax) and suppressor gene products (WT-1, RB gene, and p53) in cultured renal cell carcinoma (RCC), bladder cancer (TCC), and prostatic cancer cell lines and their MDR-sublines were studied using specific antibodies and an immunofluorescence flow cytometric method. Their relationships with development of acquired MDR in these 3 common urological cancers were analyzed.
RESULTS: Results revealed that entire sets of oncoproteins generally increased during the early phase of adriamycin challenge to RCC8701 tumor cells. In addition to the RB gene product, the response pattern dramatically changed into generally decreased expression of various oncoproteins after long-term culture. In a similar way , the TCC8803/ADR200 MDR subline of bladder cancer initially showed increased expression of oncoproteins, then a decrease to lower contents after long-term treatment with a higher concentration of adriamycin in addition to p53. On the contrary, bizarre changes in oncoproteins were observed in the prostatic cancer MDR cell line, DU145/ADR80, with increased expression of bcl-2, Bax, p53-wild, and WT-1.
CONCLUSIONS: Generally increased expression of various oncoproteins initially occurred in the development of MDR of renal and bladder cancers, while prostate cancer exhibited a more-unstable form. Persistent elevation of suppressor gene products was seen in renal and bladder cancers including RB and p53, respectively. This indicates that these suppressor oncogenes may be closely related to the generation of MDR in renal and bladder cancers.

並列關鍵字

oncoproteins ； renal cell carcinoma ； bladder cancer ； prostatic cancer