Igawa M, Rukstalis D B, Tanabe T, Chodak G W
Department of Surgery, University of Chicago, Illinois.
Cancer Res. 1994 Mar 1;54(5):1313-8.
Reduced expression of the nm23 gene has been correlated with high metastatic potential in rodent mammary tumors and human breast cancer. The expression of this gene was studied in human prostate cancer tissue from 43 patients by immunohistochemistry using anti-nm23-H1 antibodies. Intense immunostaining was observed in 71.4% of the patients with clinical stage D disease as compared to 23.1% in clinical stage B and 18.7% in stage C disease (P < 0.05). Similarly intense immunostaining was present in 75% of poorly differentiated cancers versus only 28.6% in men with moderately differentiated cancer. nm23-H1 mRNA expression was measured by Northern blot analysis during phases of the cell cycle in DU 145, PC-3, LNCaP, and TSU-Prl human prostate cancer cell lines. Cells were synchronized in G0-G1 phases by serum deprivation and at the G1-S boundary by aphidicolin. nm23-H1 mRNA levels declined during serum deprivation and increased rapidly following serum addition. Although nm23-H1 was expressed continuously throughout the cell cycle, higher expression was observed in late G1, early S, and G2-M phases. These results indicate that nm23-H1 gene expression is related to the proliferative phase of cell growth.
nm23基因表达降低与啮齿动物乳腺肿瘤和人类乳腺癌的高转移潜能相关。使用抗nm23-H1抗体通过免疫组织化学研究了43例患者的人前列腺癌组织中该基因的表达。临床分期为D期的患者中有71.4%观察到强烈免疫染色,相比之下,临床分期为B期的患者中为23.1%,C期患者中为18.7%(P<0.05)。同样,75%的低分化癌存在强烈免疫染色,而中度分化癌男性中仅为28.6%。通过Northern印迹分析在DU 145、PC-3、LNCaP和TSU-Prl人前列腺癌细胞系的细胞周期各阶段测量nm23-H1 mRNA表达。通过血清剥夺使细胞同步于G0-G1期,通过阿非科林使细胞同步于G1-S边界。血清剥夺期间nm23-H1 mRNA水平下降,血清添加后迅速升高。尽管nm23-H1在整个细胞周期中持续表达,但在G1晚期、S早期和G2-M期观察到更高的表达。这些结果表明nm23-H1基因表达与细胞生长的增殖期相关。