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人类 SBK1 在多种癌症中失调,并促进卵巢癌 SK-OV-3 细胞的存活。

Human SBK1 is dysregulated in multiple cancers and promotes survival of ovary cancer SK-OV-3 cells.

机构信息

Chinese National Human Genome Center, #3-707 North YongChang Road BDA, Beijing 100176, People's Republic of China.

出版信息

Mol Biol Rep. 2011 Jun;38(5):3551-9. doi: 10.1007/s11033-010-0465-8. Epub 2010 Nov 20.

Abstract

Protein kinases are involved in comprehensive cellular processes and also implicated in many human diseases. SH3-binding domain kinase 1 (SBK1) was first cloned and characterized in rat and the human cDNA was cloned in our lab in 2006, but the expression and function of endogenous protein have not been well studied in human. In this follow up study, we screened a panel of cell lines and tissues, as well as a tumor tissue array for SBK1 expression at both RNA and protein levels. To detect the protein, we generated the first rabbit polyclonal antibody against human SBK1. We show that the SBK1 is expressed in most of the cells and tissues examined, and the protein is highly up-regulated in ovarian serous adenocarcinoma while down-regulated in esophagus squamous cell carcinoma and stomach adenocarcinoma. When over-expressed in an ovarian cancer cells SK-OV-3 by adenovirus infection, SBK1 protected the cells from apoptosis induced by the viral infection, therefore promoting cancer cell survival. Given that a missense mutation K92E in human SBK1 was identified recently from ovarian mucinous carcinoma, together, these results suggest that the wide-spread expression pattern of human SBK1 may predict a broad cellular function, and its dysregulated in certain cancers suggests an involvement of the protein in the pathogenesis of human cancers.

摘要

蛋白激酶参与广泛的细胞过程,也与许多人类疾病有关。SH3 结合域激酶 1(SBK1)最初在大鼠中被克隆和鉴定,我们的实验室于 2006 年克隆了人类 cDNA,但内源性蛋白的表达和功能尚未在人类中得到很好的研究。在这项后续研究中,我们在 RNA 和蛋白质水平上筛选了一组细胞系和组织,以及肿瘤组织阵列,以检测 SBK1 的表达。为了检测蛋白质,我们生成了针对人 SBK1 的第一个兔多克隆抗体。我们表明,SBK1 在大多数检查的细胞和组织中表达,在卵巢浆液性腺癌中高度上调,而在食管鳞状细胞癌和胃腺癌中下调。当通过腺病毒感染在卵巢癌细胞 SK-OV-3 中过表达时,SBK1 保护细胞免受病毒感染诱导的凋亡,从而促进癌细胞存活。鉴于最近从卵巢黏液腺癌中鉴定出人 SBK1 的错义突变 K92E,这些结果表明人 SBK1 的广泛表达模式可能预示着广泛的细胞功能,而其在某些癌症中的失调表明该蛋白参与了人类癌症的发病机制。

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