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S100P蛋白的表达与宫颈癌HeLa细胞的致瘤能力相关并对其有促进作用。

Expression of S100P protein correlates with and contributes to the tumorigenic capacity of HeLa cervical carcinoma cells.

作者信息

Gibadulinová Adriana, Baráthová Monika, Kopácek Juraj, Hulíková Alzbeta, Pastoreková Silvia, Kettmann Richard, Pastorek Jaromír

机构信息

Centre of Molecular Medicine, Institute of Virology, Slovak Academy of Sciences, Dúbravská cesta 9, 84505 Bratislava, Slovak Republic.

出版信息

Oncol Rep. 2005 Aug;14(2):575-82.

Abstract

Tumor growth is associated with multiple changes at the gene expression level. Recognition of the genes differentially expressed between the cellular populations at various degrees of malignancy may provide valuable clues towards the identification of clinically useful diagnostic markers and/or therapeutic targets. In the present study, we used suppression subtractive PCR to identify differentially expressed genes with possible relevance for control of tumorigenic potential using two cervical carcinoma cell lines of the common HeLa origin, but of different capacity to generate tumors in nude mice. Screening of the subtracted libraries resulted in isolation of several known as well as novel genes including the gene encoding S100P calcium-binding protein that belongs to S100 family, whose members can bind and modulate effector proteins in a calcium-dependent manner. Expression of S100P was further studied in the context of different culture conditions and was found to correlate with the tumorigenic phenotype of the somatic cell hybrids between HeLa and normal human fibroblasts. Moreover, S100P was highly expressed in a number of tumorigenic cell lines derived from colorectal and breast carcinoma, suggesting that it is not restricted to a particular tumor type. Functional involvement of S100P in tumor growth was evaluated using tumor xenografts produced from the cells transfected with the full-length S100P cDNA. The results showed that S100P can positively affect anchorage-independent growth of the transfected cells and improve tumor formation in nude mice, suggesting that it actively participates in the control of the tumorigenic potential in vivo.

摘要

肿瘤生长与基因表达水平的多种变化相关。识别在不同恶性程度的细胞群体之间差异表达的基因,可能为鉴定临床上有用的诊断标志物和/或治疗靶点提供有价值的线索。在本研究中,我们使用抑制性消减杂交PCR技术,以两种源自常见海拉细胞系、但在裸鼠中产生肿瘤能力不同的宫颈癌细胞系,来鉴定可能与控制致瘤潜能相关的差异表达基因。对消减文库的筛选导致分离出几个已知基因和新基因,包括编码属于S100家族的S100P钙结合蛋白的基因,该家族成员能够以钙依赖方式结合并调节效应蛋白。在不同培养条件下进一步研究了S100P的表达,发现其与海拉细胞和正常人成纤维体细胞杂种的致瘤表型相关。此外,S100P在许多源自结直肠癌和乳腺癌的致瘤细胞系中高表达,表明它并不局限于特定的肿瘤类型。使用转染了全长S100P cDNA的细胞产生的肿瘤异种移植模型,评估了S100P在肿瘤生长中的功能作用。结果表明,S100P可以正向影响转染细胞的非锚定依赖性生长,并改善裸鼠中的肿瘤形成,表明它在体内积极参与致瘤潜能的控制。

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