突变基因编码的分析urokinase-type纤溶酶原激活物(uPA)及其抑制剂PAI-1在晚期卵巢癌。
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土库曼B,施密特M, Schmalfeldt B,一张P,地狱W, Creutzburg年代,Graeff H, Magdolen V
突变基因编码的分析urokinase-type纤溶酶原激活物(uPA)及其抑制剂PAI-1在晚期卵巢癌。
电泳。1997;18 (5):686 - 9。
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9194591 (在PubMed]
- 文摘
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积累的证据表明urokinase-type纤溶酶原激活物(uPA),其抑制剂(PAI-1)和受体(uPAR)参与肿瘤的浸润和转移。我们分析了DNA序列编码这些因素是否改变在卵巢癌细胞株OV-MZ-6 OV-MZ-19, OVCAR-3。uPA-encoding cDNA源自OV-MZ-6细胞(而不是uPA-cDNA OVCAR-3和OV-MZ-19),一位至今未知突变被发现在121密码子,导致脯氨酸,亮氨酸交换。这种交流创造了一个AluI限制网站制作限制片段长度多态性(RFLP)分析成为可能。以前公布PAI-1序列指着PAI-1信号序列的变异氨基酸15代表苏氨酸或丙氨酸,在目前的研究证实。的uPAR互补编码的所有三个细胞株发布的野生型序列。为了阐明Pro121Leu交换的可能角色uPA和阿拉巴马州/刺信号序列的变异PAI-1开发和/或人类卵巢癌进展,我们研究了这些突变体的存在或变异的一系列22卵巢癌组织。除了野生型序列,uPA Pro121Leu交易所序列中检测出10个22肿瘤组织;11肿瘤进行专门Pro121等位基因;在一个案例中只Leu121等位基因检测。 In 18/22 tumors, triplet 15 in the signal sequence of PAI-1 encoded alanine, four DNAs contained both the Ala and the Thr allele. Furthermore, we analyzed another known common single-base-pair insertion/deletion polymorphism (ins/del allele) found in the promoter region of the PAI-1 gene and thought to be of functional importance in regulating PAI-1 gene expression. The PAI-1 ins-allele was found in 3/22, the del-allele in 6/22 and both alleles in 13/22 ovarian cancer tissues. In genomic DNA isolated from peripheral blood of 23 healthy donors, we observed similar allele frequencies of the three polymorphisms as found in the 22 ovarian carcinomas. Taken together, these results suggest that the polymorphisms observed in the uPA and PAI-1 genes may not be linked to ovarian cancer.