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      • N-butyl-N-(4-hydroxybutyl) nitrosamine에 의한 흰쥐 방광암 발생과정에서 c-erbB-2 종양단백, 증식성 핵항원(PCNA)과 Apoptosis의 평가

        박원주 중앙대학교 의과대학 의학연구소 2005 中央醫大誌 Vol.30 No.1

        c-erbB-2 is a proto-oncogene that closely related to the epidermal growth factor receptor and plays an important role in carcinogenesis. Apoptosis and cell proliferation play a major roles in chemical multistage carcinogenesis. This study analyzed the status of c-erbB-2, apoptosis, and proliferating cell nuclear antigen (PCNA) during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat urinary bladder carcinogenesis. For sequential histopathological findings of urinary bladder, 0.05% BBN was administered to male rats in 30 weeks. To detect protein expressions of c-erbB-2 and PCNA, immunohistochemical stains were used. Also apoptosis identified morphologically and TdT-mediated dUTP-biotin nick end labeling (TUNEL) were used. On histopathological findings, urothelial cell hyperplasia was appeared at 5 weeks, followed by urothelial papilloma at 10 weeks, and superfical urothelial carcinoma was found at 20 weeks after BBN administration. After 30 weeks of BBN administration, invasive carcinoma was developed in 40% (4/10) among the all 10 cancer rats. The immunohistochemical stains for c-erbB-2 did not expressed in normal urinary bladder. Overexpression of c-erbB-2 were observed along the cell membrane in urothelial cell hyperplasia and papilloma. Reduced expression of c-erbB-2 were found in both superficial and invasive carcinomas. The PCNA and apoptotic labeling indices were very low in normal bladder epithelia. With the lesions progressed from urothelial cell hyperplasia to papilloma to urothelial carcinoma, the PCNA and apoptotic labeling indices significantly increased (P<0.01). There was no correlation between PCNA, apoptosis indices and c-erbB-2 expression. The present results indicate that c-erbB-2 may participates the early stage of carcinogenesis and hyperproliferative cells might be more susceptible to apoptosis. Also, the numbers of the PCNA and apoptosis could be useful markes for evaluating the risk of malignant transformation of transitional cell carcinoma of the urinary bladder.

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