Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumours.

Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumours.
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DOI:
10.1038/bjc.1997.258
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发表时间:
1997
影响因子:
8.8
通讯作者:
Chrétien M
Chrétien M
中科院分区:
医学1区
文献类型:
--
作者:
Mbikay M;Sirois F;Yao J;Seidah NG;Chrétien M

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前蛋白转化酶通过其前体的有限蛋白水解介导多种肽有丝分裂原的产生。这些蛋白酶也可能参与癌细胞自分泌产生这些有丝分裂原,从而促进这些细胞的不受抑制的增殖。作为确定这种贡献的一个步骤,我们使用半定量北方印迹分析检测了人肺肿瘤中四种转化酶mRNA的水平。弗林蛋白酶mRNA表达在所有的肿瘤,其水平在鳞状细胞癌和腺癌的平均约三倍高于小细胞肺癌(SCLC)。在14例腺癌中的8例和17例鳞状细胞癌中的7例中检测到PACE 4转录物;在7例SCLC中仅2例可检测到PACE 4转录物。PC 1 mRNA未检测到鳞状细胞癌和所有,但两个腺癌,它存在于四个六SCLC。PC 2 mRNA在两个腺癌,一个鳞状细胞癌和7个SCLC中的5个中被发现。这项初步调查表明,小细胞肺癌往往携带更多的mRNA的内分泌转化酶PC 1和PC 2和更普遍的弗林蛋白酶和PACE 4的mRNA较少,这表明这些转化酶在这种肿瘤的发展中的反向作用。
Proprotein convertases mediate the production of a variety of peptidic mitogens by limited proteolysis of their precursors. These proteases may also participate in the autocrine production of such mitogens by cancer cells and thus contribute to the unchecked proliferation of these cells. As a step towards defining this contribution, we have examined the levels of four convertase mRNAs in human lung neoplasms using semiquantitative Northern blot analysis. Furin mRNA was expressed in all the tumours; its level in squamous cell carcinomas and adenocarcinomas was on average about threefold higher than in small-cell lung carcinomas (SCLCs). PACE4 transcripts were detected in eight of 14 adenocarcinomas and in seven of 17 squamous cell carcinomas; they were detectable in only two of seven SCLCs. PC1 mRNA was undetected in squamous cell carcinomas and in all but two adenocarcinomas; it was present in four of six SCLCs. PC2 mRNA was found in two adenocarcinomas, in one squamous cell carcinoma and in five of seven SCLCs. This preliminary survey indicates that SCLCs often carry more mRNA for the endocrine convertases PC1 and PC2 and less mRNA for the more ubiquitous furin and PACE4, suggesting inverse roles of these convertases in the development of this neoplasm.