Naito S, Shimizu K, Nakashima M, Nakayama T, Ito T, Ito M, Yamashita S, Sekine I
Tissue and Histopathology Section, Nagasaki University School of Medicine, Japan.
Pathol Res Pract. 2000;196(2):103-9. doi: 10.1016/S0344-0338(00)80041-2.
Angiosarcoma of the skin is a rare malignant tumor which is slow-growing but highly aggressive and often recurs following surgery and/or radiation therapy, finally metastasizing to the regional lymph nodes. The ets-1 protooncogene is shown to be transcribed in endothelial cells during angiogenesis in granulation tissue and in malignant cells during tumor invasion. Furthermore, it can regulate the expression of metalloproteinase genes such as collagenase-1 (MMP-1), stromelysin (MMP-3) and urokinase-type plasminogen activator (uPA). In this study we investigated the ets-1 and MMP-1 expression in 7 angiosarcomas of the skin, compared with 7 hemangiomas and 7 granuloma pyogenicums of the skin, which are well known as benign vascular diseases. The ets-1 and MMP-1 mRNAs and their proteins were overexpressed in all angiosarcomas tested, and the localization of MMP-1 expression corresponded to that of ets-1. On the other hand, they were weakly or not at all expressed in hemangiomas and granuloma pyogenicums. These results suggest that the constitutive overexpression of ets-1 might be closely related with the malignant progression of angiosarcoma, possibly through the up-regulation of the transcription of MMP-1.
皮肤血管肉瘤是一种罕见的恶性肿瘤，生长缓慢但侵袭性强，手术后和/或放疗后常复发，最终转移至区域淋巴结。研究表明，ets-1原癌基因在肉芽组织血管生成过程中的内皮细胞以及肿瘤侵袭过程中的恶性细胞中均有转录。此外，它还可以调节金属蛋白酶基因的表达，如胶原酶-1（MMP-1）、基质溶解素（MMP-3）和尿激酶型纤溶酶原激活剂（uPA）。在本研究中，我们调查了7例皮肤血管肉瘤中ets-1和MMP-1的表达情况，并与7例血管瘤和7例皮肤化脓性肉芽肿进行了比较，后两者均为众所周知的良性血管疾病。在所检测的所有血管肉瘤中，ets-1和MMP-1的mRNA及其蛋白均过度表达，且MMP-1表达的定位与ets-1一致。另一方面，它们在血管瘤和皮肤化脓性肉芽肿中表达较弱或根本不表达。这些结果表明，ets-1的组成性过表达可能与血管肉瘤的恶性进展密切相关，可能是通过上调MMP-1的转录实现的。
