Expression of low molecular G protein Rho family in renal cell carcinoma

肾细胞癌（RCC）是一种发生于近端肾小管上皮的人类肾癌，约占成人恶性肿瘤的3%。RCC是高度恶性的肿瘤，通常扩散到肾脏以外。先前已经表征了可能有助于RCC中恶性细胞转化过程的几个因素，包括吸烟、肥胖、高血压、化学试剂、遗传学和终末期肾病。RCC从正常肾上皮的发展可能涉及基因的改变，如VHL，p53和Ras，其产物控制细胞分裂。Rho家族是Ras超家族的一个亚家族，其中RhoA、Rac 1和Cdc 42蛋白被广泛研究。它们在肌动蛋白细胞骨架的组织和细胞粘附，以及增殖、基因表达和细胞周期调节中起重要作用。 ...更多信息 是的。我们已经分离出一种新的人cDNA编码的人耐盐蛋白（HSTP），这是一个同源的大鼠耐盐蛋白（STP）。STP主要位于近端小管，由高盐负荷诱导，并以某种方式与细胞内阳离子稳态相互作用。HSTP cDNA的核苷酸序列（1988 bp）含有一个开放阅读框，编码由545个氨基酸组成的多肽，与人CIP 4的核苷酸同源性高达98%，CIP 4与Cdc 42的活性GTP结合构象特异性结合。我们在这里报告，我们已经确定了一个突变的HSTP基因在肾细胞癌（RCC）的患者，百分之五十（15 29）的RCC检查显示异常剪接事件在逆转录（RT）-PCR和插入19个核苷酸的序列分析中来自内含子9。该突变体编码提前终止密码子，导致SH 3结构域和Cdc 42结合结构域的丢失。HSTP可能通过影响肌动蛋白细胞骨架而参与肾细胞癌的发生和侵袭。少

Renal cell carcinoma (RCC), a human kidney cancer from the proximal tubular epithelium, accounts for about 3% of adult malignancies. RCC are highly malignant tumors and often spread beyond the kidney. Several factors that may contribute to the process of malignant cell transformation in RCC have previously been characterized, and include cigarette smoking, obesity, hypertension, chemical agents, genetics and end-stage renal disease. The development of RCC from normal renal epithelium may involve alterations in genes, such as VHL, p53 and Ras, whose products control cell division. However, the pathogenic mechanisms that promote tumor progression, invasion and metastasis, have not yet been defined.The Rho family is a subgroup of the Ras superfamily, in which the RhoA, Rac1 and Cdc42 proteins have been most extensively characterized. They play an essential role in the organization of the actin cytoskeleton and cell adhesion, as well as proliferation, gene expression, and cell cycle regula … More tion. We have isolated a novel human cDNA coding for human salt-tolerant protein (HSTP), which is a homologue of the rat salt-tolerant protein (STP). STP is localized mainly in the proximal tubules, is induced by high-salt loading, and somehow interacts with intracellular cation homeostasis. The nucleotide sequence (1988bp) of the HSTP cDNA contains an open reading frame encoding a polypeptide that consist of 545 amino acids and shows a high degree (98%) of nucleotide identity to human CIP4, which binds specifically to the active GTP-bound conformation of Cdc42. We report here that we have identified a mutation in the HSTP gene in patients with renal cell carcinoma (RCC); fifty percent (15 of 29) of RCCs examined showed an aberrant splicing event in reverse transcription (RT)-PCR and the insertion of 19 nucleotides derived from intron9 in a sequence analysis. This mutant encodes a premature stop codon, resulting in loss of the SH3 domain and Cdc42 binding domain. HSTP may be involved in the tumorigenesis and invasiveness of RCC, probably through its effects on the actin cytoskeleton. Less