Hofmann M C, Jeltsch W, Brecher J, Walt H
Institute of Pathology, University of Zürich, Switzerland.
Cancer Res. 1989 Sep 1;49(17):4696-700.
The four known isozymes of the human alkaline phosphatase (ALP) were detected by isoelectric focusing in extracts of various types of germ cell tumors, three related cell lines, and their precancerous elements (atypical germ cells). In seminoma, placental alkaline phosphatase (PLAP) and germ cell alkaline phosphatase (PLAP-like) could be separated by isoelectric focusing following isolation by immunoaffinity. The occurrence of both isozymes in seminoma could explain partial heat sensitivity and variation in electrophoretic patterns of the seminoma isozyme frequently observed upon starch gels, in comparison to the normal placental phenotype. The four ALP isozymes are produced not only in germ cell tumors, but already in precancerous tissues. Quantitative analysis showed that the amount of the four isozymes varies in parallel in the tumors tested. Maximal expression was found in seminoma. The relation between ALP gene overexpression and gene amplification by polyploidy of chromosomes 1 and 2 in these lesions is discussed. On the other hand, the ectopic expression of intestinal alkaline phosphatase and PLAP associated with overexpression of PLAP-like in tumor cells as well as in their precancerous stage indicates gene activation by some unknown mechanisms, probably a regulatory process affecting the three tissue-specific ALP genes simultaneously.
通过等电聚焦法,在各种类型的生殖细胞肿瘤、三种相关细胞系及其癌前成分(非典型生殖细胞)的提取物中检测到了人类碱性磷酸酶(ALP)的四种已知同工酶。在精原细胞瘤中,胎盘碱性磷酸酶(PLAP)和生殖细胞碱性磷酸酶(类PLAP)在通过免疫亲和分离后,可通过等电聚焦法分离。与正常胎盘表型相比,精原细胞瘤中这两种同工酶的存在可以解释精原细胞瘤同工酶在淀粉凝胶上经常观察到的部分热敏感性和电泳图谱的变化。这四种ALP同工酶不仅在生殖细胞肿瘤中产生,在癌前组织中就已产生。定量分析表明,在所测试的肿瘤中,这四种同工酶的量平行变化。在精原细胞瘤中发现了最大表达。讨论了这些病变中ALP基因过表达与1号和2号染色体多倍体导致的基因扩增之间的关系。另一方面,肿瘤细胞及其癌前阶段中肠碱性磷酸酶和PLAP的异位表达与类PLAP的过表达相关,这表明通过一些未知机制激活了基因,可能是一个同时影响三个组织特异性ALP基因的调控过程。