Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor.
Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor.
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DOI：
10.1681/asn.v9101873
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发表时间：
1998-10
期刊：
影响因子：
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通讯作者：
Sara G. Carlson;Eudora Eng;Eung-Gook Kim;Elizabeth J. Perlman;Terry D. Copeland;Barbara J. Ballermann
中科院分区：
文献类型：
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作者：
Sara G. Carlson;Eudora Eng;Eung-Gook Kim;Elizabeth J. Perlman;Terry D. Copeland;Barbara J. Ballermann
人类基因集最初被确定为急性未分化白血病病例中体细胞易位事件产生的SET-CAN融合基因的一个组成部分。在发育中的肾脏中，SET在肾单位形态发生区高表达。最近，SET被证明是一种有效和特异的蛋白磷酸酶2A的抑制剂，蛋白磷酸酶是一类主要的丝氨酸/苏氨酸磷酸酶家族，参与调节细胞的增殖和分化。目前的研究试图进一步确定SET在调节肾细胞增殖和肿瘤发生中的作用。该基因在转化的人和啮齿动物细胞系中的表达水平明显高于培养的肾上皮细胞和原代内皮细胞。与SET在细胞增殖中的作用一致，在因血清饥饿、接触抑制或分化而处于静止状态的细胞中，SET mRNA的表达显著减少。之前在肾脏发育过程中的发现得到了扩展，证明SET蛋白在发育中的大鼠和人类肾脏中的表达也比在完全分化的成熟肾脏中要高得多。肾母细胞瘤中有较高水平的SET mRNA和SET蛋白表达，而肾细胞癌、成人多囊肾病和移行细胞癌中未见表达。
The human gene set was originally identified as a component of the set-can fusion gene produced by a somatic translocation event in a case of acute undifferentiated leukemia. In the developing kidney, set was highly expressed in the zone of nephron morphogenesis. Recently, SET was shown to be a potent and specific inhibitor of protein phosphatase 2A, a family of major serine/threonine phosphatases involved in regulating cell proliferation and differentiation. The current study sought to define further the role of SET in the regulation of renal cell proliferation and tumorigenesis. The mRNA encoding SET was expressed at much higher levels in transformed human and rodent cell lines than in cultured renal epithelial and primary endothelial cells. Consistent with a role for SET in cell proliferation, set mRNA expression was markedly reduced in cells rendered quiescent by serum starvation, contact inhibition, or differentiation. Previous findings during renal development were extended by demonstrating that SET protein expression is also much greater in developing rat and human kidney than in fully differentiated, mature kidney. Finally, high levels of set mRNA and SET protein expression were found in Wilms' tumor, but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma.