Expression of ADAM-9 mRNA and protein in human breast cancer

Expression of ADAM-9 mRNA and protein in human breast cancer
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DOI:
10.1002/ijc.11161
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发表时间:
2003-07-20
影响因子:
6.4
通讯作者:
Duffy, MJ
Duffy, MJ
中科院分区:
医学1区
文献类型:
--
作者:
O'Shea, C;McKie, N;Duffy, MJ

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亚当斯(一种去整合素和金属蛋白酶)是同时含有蛋白酶和粘附结构域的膜蛋白,因此可能在癌症侵袭和转移中具有潜在的重要性。本研究旨在探讨ADAM-9在乳腺癌组织中的表达及其临床意义。ADAM-9的表达采用逆转录聚合酶链反应(RTPCR)和蛋白质印迹法。与正常乳腺组织(6125,24%)相比,ADAM-9 mRNA在乳腺癌(72/110,66%)和纤维腺瘤(21/38,SS%)中表达更频繁(分别为p = 0.0004,p = 0.028)。通过Western印迹检测到多种形式的ADAM-9蛋白,即,在还原条件下为124、84和48 kDa,在非还原条件下为115、76、55、52和46 kDa。与正常乳腺组织相比,在原发性癌症中更频繁地检测到84和55 kDa形式(分别为p < 0.0001,p = 0.0002)。此外,84 kDa成熟形式的相对水平在原发性癌症中显著高于纤维腺瘤(p = 0.003),而124 kDa前体形式则相反(p = 0.026)。在癌中,84 kDa形式的ADAM-9蛋白在淋巴结阳性癌中的表达水平高于淋巴结阴性癌(p = 0.05),并且与HER-2/neu蛋白水平呈正相关(r = 0.313,p = 0.016)。这是第一个报告,以描述任何ADAM在大量的人类癌的表达。(C)2003 Wiley-Liss,Inc.
The ADAMs (a disintegrin and metalloprotease) are membrane proteins containing both protease and adhesion domains and thus may be potentially important in cancer invasion and metastasis. The aim of our study was to investigate the distribution and potential clinical significance of ADAM-9 in breast cancer. ADAM-9 expression was measured using both reverse transcriptase-polymerase chain reaction (RTPCR) and Western blotting. ADAM-9 mRNA was expressed more frequently in both breast carcinomas (72/110, 66%) and fibroadenomas (21/38, SS%) compared, to normal breast tissue (6125, 24%) (p = 0.0004, p = 0.028, respectively). Multiple forms of ADAM-9 protein were detected by Western blotting, i.e., at 124, 84 and 48 kDa under reducing conditions and at I IS, 76, 55, 52 and 46 kDa under nonreducing conditions. The 84 and 55 kDa forms were detected more frequently in the primary cancers compared to normal breast tissue (p < 0.0001, p = 0.0002, respectively). In addition, relative levels of the 84 kDa mature form were significantly higher in, the primary cancers than in the fibroadenomas (p = 0.003), while the reverse was found for the 124 kDa precursor form (p = 0.026). In the carcinomas, the 84 kDa form of ADAM-9 protein was expressed at higher levels in node-positive than node-negative cancers (p = 0.05) and correlated positively with HER-2/neu protein levels (r = 0.313, p = 0.0 16). This is the first report to describe expression of any ADAM in a large number of human carcinomas. (C) 2003 Wiley-Liss, Inc.