Porter Sarah, Scott Stuart D, Sassoon Elaine M, Williams Mark R, Jones J Louise, Girling Anne C, Ball Richard Y, Edwards Dylan R
School of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
Clin Cancer Res. 2004 Apr 1;10(7):2429-40. doi: 10.1158/1078-0432.ccr-0398-3.
The adamalysin-thrombospondin (ADAMTS) proteinases are a relatively newly described branch of the metzincin family that contain metalloproteinase, disintegrin, and thrombospondin motifs. They have been implicated in various cellular events, including cleavage of proteoglycans, extracellular matrix degradation, inhibition of angiogenesis, gonadal development, and organogenesis. However, in many cases, their normal physiological roles and their potential for dysregulation in malignancy remain to be established. The expression profile of ADAMTS1-20 in human breast carcinoma was undertaken by real-time PCR using RNA isolated from malignant tumors, nonneoplastic mammary tissue, and breast cancer cell lines to identify altered regulation that may have potential pathogenetic and prognostic significance. Our studies show that seven of the ADAMTS genes (ADAMTS1, 3, 5, 8, 9, 10, and 18) are consistently down-regulated in breast carcinomas with respect to nonneoplastic mammary tissue, irrespective of the heterogeneity of the samples and the tumor type or grade (Mann-Whitney U test, P < 0.0001 for each gene). Conversely, ADAMTS4, 6, 14, and 20 are consistently up-regulated in breast carcinomas (P = 0.005, P < 0.0001, P = 0.003, and P = 0.001, respectively). ADAMTS2, 7, 12, 13, 15, 16, 17, and 19 show no significant difference between the sample types. ADAMTS1, 2, 7, 8, 10, and 12 are expressed predominantly in stromal fibroblasts. ADAMTS3, 4, 5, 6, 9, and 13-20 inclusive are expressed predominantly in myoepithelial cells; all appear to be relatively poorly expressed in luminal epithelial cells. ADAMTS15 has emerged as being an independent predictor of survival, with RNA expression levels significantly lower (P = 0.007) in grade 3 breast carcinoma compared with grade 1 and 2 breast carcinoma.
解聚素和金属蛋白酶凝血酶敏感蛋白（ADAMTS）蛋白酶是金属锌蛋白酶家族中一个相对较新描述的分支，包含金属蛋白酶、解聚素和凝血酶敏感蛋白基序。它们参与了各种细胞活动，包括蛋白聚糖的裂解、细胞外基质降解、血管生成抑制、性腺发育和器官发生。然而，在许多情况下，它们的正常生理作用以及在恶性肿瘤中失调的可能性仍有待确定。利用从恶性肿瘤、非肿瘤性乳腺组织和乳腺癌细胞系中分离的RNA，通过实时PCR对人乳腺癌中ADAMTS1 - 20的表达谱进行分析，以确定可能具有潜在致病和预后意义的调控改变。我们的研究表明，与非肿瘤性乳腺组织相比，七种ADAMTS基因（ADAMTS1、3、5、8、9、10和18）在乳腺癌中始终下调，无论样本的异质性以及肿瘤类型或分级如何（Mann - Whitney U检验，每个基因P < 0.0001）。相反，ADAMTS4、6、14和20在乳腺癌中始终上调（分别为P = 0.005、P < 0.0001、P = 0.003和P = 0.001）。ADAMTS2、7、12、13、15、16、17和19在样本类型之间无显著差异。ADAMTS1、2、7、8、10和12主要在基质成纤维细胞中表达。ADAMTS3、4、5、6、9以及包括13至20在内的基因主要在肌上皮细胞中表达；在管腔上皮细胞中似乎都表达相对较低。ADAMTS15已成为生存的独立预测因子，与1级和2级乳腺癌相比，3级乳腺癌中的RNA表达水平显著降低（P = 0.007）。
