Tsuda H, Asamoto M, Baba H, Iwahori Y, Matsumoto K, Iwase T, Nishida Y, Nagao S, Hakoi K, Yamaguchi S
Chemotherapy Division, National Cancer Center Research Institute, Tokyo, Japan.
Carcinogenesis. 1995 Jan;16(1):101-5. doi: 10.1093/carcin/16.1.101.
The expression of connexin 32 (Cx32), a major liver gap junction protein, after partial hepatectomy (PH) and during development and progression of hepatocarcinogenesis was studied in the rat. Cx32 was quantitatively analyzed by counting immunohistochemically demonstrated protein spots on the membranes of hepatocytes. Livers were sequentially examined after PH to assess the correlation with cell proliferation. For the analysis of different stages in carcinogenesis, Cx32 was assayed in N-ethyl-N-hydroxyethylnitrosamine-induced enzyme altered foci (EAF), hyperplastic nodules (HN), hepatocellular carcinomas (HCC), pulmonary metastatic HCC and transplanted HCC in relation to their degree of altered enzyme expression. Cx32 showed: (i) a rapid decrease after PH to its lowest levels during and 12 h after the S phase of cell proliferation when 5-bromo-2'-deoxyuridine (BrdU) labeling indices were examined; (ii) a progressive decrease from early preneoplasia EAF to HN and HCC, values for pulmonary metastatic and transplanted HCC being 0; (iii) clearly inverse correlations with increased BrdU index and degree of altered enzyme expression in HN, indicating that these, with the lowest Cx32 count, are closest to HCC. Therefore, the observed decrease appears linked to cell proliferation and progression of hepatocarcinogenesis, providing a reflection of cellular independence and growth advantage.
在大鼠中研究了主要的肝脏缝隙连接蛋白连接蛋白32（Cx32）在部分肝切除（PH）后以及肝癌发生发展过程中的表达情况。通过对免疫组织化学显示的肝细胞细胞膜上的蛋白斑点进行计数，对Cx32进行定量分析。在PH后对肝脏进行连续检查，以评估其与细胞增殖的相关性。为了分析致癌作用的不同阶段，检测了N-乙基-N-羟乙基亚硝胺诱导的酶改变灶（EAF）、增生性结节（HN）、肝细胞癌（HCC）、肺转移性HCC和移植性HCC中Cx32的表达，并与其酶表达改变程度相关联。Cx32表现出：（i）PH后迅速下降至细胞增殖S期期间及之后12小时的最低水平，此时检测了5-溴-2'-脱氧尿苷（BrdU）标记指数；（ii）从早期癌前EAF到HN和HCC逐渐下降，肺转移性和移植性HCC的值为0；（iii）与HN中BrdU指数增加和酶表达改变程度呈明显负相关，表明这些BrdU指数最低且Cx32计数最低的情况最接近HCC。因此，观察到的下降似乎与细胞增殖和肝癌发生发展相关，反映了细胞的独立性和生长优势。
