Tanimoto H, Yan Y, Clarke J, Korourian S, Shigemasa K, Parmley T H, Parham G P, O'Brien T J
Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, Little Rock 72205-7199, USA.
Cancer Res. 1997 Jul 15;57(14):2884-7.
Extracellular proteases mediate the digestion of neighboring extracellular matrix components in initial tumor growth, allow shedding or desquamation of tumor cells into the surrounding environment, provide the basis for invasion of basement membranes in target metastatic organs, and are required for release and activation of many growth and angiogenic factors. We identified overexpression of the serine protease hepsin gene in ovarian carcinomas and investigated the expression of this gene in 44 ovarian tumors (12 low malignant potential tumors and 32 carcinomas) and 10 normal ovaries. Quantitative PCR was used to determine the relative expression of hepsin compared to that of beta-tubulin. The mRNA expression levels of hepsin were significantly elevated in 7 of 12 low malignant potential tumors and in 27 of 32 carcinomas. On Northern blot analysis, the hepsin transcript was abundant in carcinoma but was almost never expressed in normal adult tissue, including normal ovary. Our results suggest that hepsin is frequently overexpressed in ovarian tumors and therefore may be a candidate protease in the invasive process and growth capacity of ovarian tumor cells.
细胞外蛋白酶在肿瘤初期生长过程中介导邻近细胞外基质成分的消化，使肿瘤细胞脱落或剥脱进入周围环境，为肿瘤细胞侵袭靶转移器官的基底膜提供基础，并且是许多生长因子和血管生成因子释放及激活所必需的。我们发现丝氨酸蛋白酶hepsin基因在卵巢癌中过表达，并研究了该基因在44例卵巢肿瘤（12例低恶性潜能肿瘤和32例癌）及10例正常卵巢中的表达情况。采用定量PCR测定hepsin相对于β-微管蛋白的相对表达量。12例低恶性潜能肿瘤中有7例以及32例癌中有27例hepsin的mRNA表达水平显著升高。Northern印迹分析显示，hepsin转录本在癌组织中丰富，但在包括正常卵巢在内的正常成人组织中几乎从不表达。我们的结果表明，hepsin在卵巢肿瘤中经常过表达，因此可能是卵巢肿瘤细胞侵袭过程和生长能力中的一种候选蛋白酶。
