Lendeckel Uwe, Kohl Jana, Arndt Marco, Carl-McGrath Stacy, Donat Hans, Röcken Christoph
Institute of Experimental Internal Medicine, Otto-von-Guericke-University, Leipziger Strasse 44, 39120, Magdeburg, Germany.
J Cancer Res Clin Oncol. 2005 Jan;131(1):41-8. doi: 10.1007/s00432-004-0619-y. Epub 2004 Sep 30.
ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer.
Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis.
Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody.
The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.
解聚素和金属蛋白酶（ADAMs）是多功能的膜结合细胞表面糖蛋白，在细胞生长、分化和运动中具有多种功能。我们希望研究ADAM 9、10、12、15在人类乳腺癌中的表达情况。
通过定量逆转录聚合酶链反应（RT-PCR）和免疫组织化学法，测定了24例患者乳腺癌标本及相应的非肿瘤性乳腺组织中ADAMs的表达，以及MCF-7和MDA-MB 453乳腺癌细胞系中ADAMs的表达。通过测量DNA合成来评估抗ADAM抗体对细胞增殖的影响。
乳腺癌组织样本显示ADAM 9、12和17的mRNA表达增加，而ADAM 10和15的表达无差异。通过免疫组织化学研究蛋白表达。所有ADAMs均在MCF-7和MDA-MB453细胞系中表达，其中ADAM 9、12和17的表达水平最高。应用抗ADAM 15和抗ADAM 17抗体可显著抑制MCF-7和MDA-MB453乳腺癌细胞系的增殖。相反，给予抗ADAM 12抗体似乎可刺激MCF-7细胞的生长。
本研究结果表明，ADAMs在人类乳腺癌中存在差异表达，并且能够调节肿瘤细胞的生长。
