Loss of tumor suppressor protein PTEN during renal carcinogenesis
Loss of tumor suppressor protein PTEN during renal carcinogenesis
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DOI：
10.1002/ijc.10303
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发表时间：
2002-05-01
影响因子：
6.4
通讯作者：
Thüroff, JW
中科院分区：
文献类型：
--
作者：
Brenner, W;Färber, G;Thüroff, JW
肿瘤抑制基因PTEN（从10号染色体缺失的磷酸酶和张力蛋白同源物）编码影响细胞增殖、凋亡和迁移的双重特异性蛋白和磷脂磷酸酶。在我们的研究中，我们研究了肾癌发生过程中PTEN的蛋白表达。使用蛋白质印迹分析检测了42例透明细胞肾细胞癌（ccRCC）和嗜酸细胞瘤以及相同患者的相应正常肾组织中的PTEN蛋白水平。免疫组化分析细胞定位。PTEN在所有研究的正常肾组织标本中均呈高表达。免疫组织化学分析显示，近端小管上皮细胞几乎完全染色，已知其为ccRCC的前体细胞。在近端小管细胞内，PTEN表现出膜为主的免疫染色模式。在ccRCC中，与正常组织相比，PTEN表达显著降低至平均小于10%，如通过蛋白质印迹分析所证明的（p < 0.001）。在高分化（G1）癌和低分化（G2-G4）癌中的减少程度相似。这些观察结果通过免疫组织化学研究再现，其揭示了ccRCC中特征性膜主导免疫染色模式的丧失。与PTEN阳性的近端小管上皮细胞相反，远端小管上皮细胞，其是良性嗜酸细胞瘤的前体细胞，仅表现出非常弱的PTEN表达。与远端小管上皮细胞相比，嗜酸细胞瘤中未发现PTEN表达下调。我们的结论是，在早期肾细胞癌变过程中，PTEN表达和PTEN膜定位丢失，因此可能是一个有价值的RCC肿瘤标志物。(C)2002 Wiley-Liss，Inc.
The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted from chromosome 10) encodes a dual specific protein and phospholipid phosphatase that affects cell proliferation, apoptosis and migration. In our study, we examined protein expression of PTEN in renal carcinogenesis. PTEN protein levels were examined in 42 clear cell renal cell carcinomas (ccRCC) and oncocytomas as well as in the corresponding normal renal tissue of the same patients using Western blot analysis. Cellular localization was analyzed by lmmunohistochemistry. PTEN was highly expressed in all investigated normal renal tissue specimens. Immunohistochemical analysis showed an almost exclusive staining of proximal tubulus epithelial cells known to be precursor cells of ccRCC. Within the proximal tubulus cells, PTEN exhibited a membrane predominant immunostaining pattern. In ccRCCs PTEN expression was markedly reduced to an average of less than 10% compared with normal tissue as evidenced by Western blot analysis (p < 0.001). The degree of reduction was similar in highly differentiated (G 1) carcinomas and in less differentiated (G2-G4) carcinomas. These observations were reproduced by immunohistochemical studies, which revealed a loss of the characteristic membrane predominant immunostaining pattern in ccRCC. In contrast to the PTEN positive proximal tubulus epithelial cells, the distal tubulus epithelial cells, which are precursor cells of the benign oncocytomas, exhibited only a very weak PTEN expression. Compared with the distal tubulus epithelial cells, no downregulation of PTEN was seen in oncocytomas. We conclude that PTEN expression and PTEN membrane localization are lost during early renal cell carcinogenesis and may therefore be a valuable RCC tumor marker. (C) 2002 Wiley-Liss, Inc.