高遷移率族蛋白B1（high mobility group protein，HMGB1）是一種高度保守的核蛋白,，廣泛分布于哺乳動物細胞,。隨著其晚期促炎作用的發(fā)現(xiàn),，HMGB1成為近年來危重醫(yī)學(xué)研究的熱點之一。
近日Oncol Lett雜志上刊登的一則研究歸納總結(jié)了HMGB1蛋白與癌癥發(fā)展之間的關(guān)系,。 研究人員總結(jié)認(rèn)為HMGB1表達的升高與某些原發(fā)性腫瘤類型包括惡性黑色素瘤、結(jié)腸癌,、前列腺癌,、胰腺癌和乳腺癌等都有關(guān)，并在大多數(shù)情況下,，HMGB1的表達水平與腫瘤細胞的侵襲和轉(zhuǎn)移能力呈正相關(guān)性,。
HMGB1通過與晚期糖化終產(chǎn)物受體（RAGE）相互作用來發(fā)揮促腫瘤作用。有些數(shù)據(jù)表明,，RAGE和HMGB1表達升高不一定是腫瘤發(fā)展、預(yù)后差的一個先決條件,，配體/受體的細胞定位也需要考慮,。但這些數(shù)據(jù)只關(guān)注了HMGB1蛋白以及其受體RAGE在各種組織和腫瘤細胞中的整體表達情況。然而,，并沒有提及他們的細胞定位情況,，也沒有提供直接證據(jù)能證明兩者之間能形成絡(luò)合物。
而在本研究中,，研究人員著重分析大鼠各個器官中HMGB1及其受體RAGE的分布,，對照組為Guerin腹水腫瘤細胞。在正常組織中,，HMGB1蛋白質(zhì)以其可溶性形式存在,，而在腫瘤細胞中，他們是不溶性,、具有結(jié)合細胞膜能力的形似存在,。HMGB1主要于與RAGE形成穩(wěn)定的蛋白片段絡(luò)合物，存在于癌細胞膜上,。（生物谷：Bioon.com）
doi:10.3892/ol.2011.459
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High mobility group B1 protein interacts with its receptor RAGE in tumor cells but not in normal tissues.
Todorova J, Pasheva E.
The high mobility group box 1 (HMGB1) protein is an abundant non-histone component of chromatin well known for its two DNA binding domains, HMG box A and HMG box B. The main characteristics of the HMGB1 protein as an 'architectural' factor are its ability to recognize and bind with high affinity to distorted DNA and its ability to induce kinks in linear DNA fragments. The HMGB1 protein has been correlated to cancer progression. An elevated expression of HMGB1 occurred in certain types of primary tumor, including melanoma and colon, prostate, pancreatic and breast cancers, and in the majority of cases HMGB1 is associated with invasion and metastasis. The main signaling pathway is activated through the interaction of HMGB1 with its Receptor for Advanced Glycation End products (RAGE). Certain data indicate that an elevated expression of RAGE and HMGB1 is not always a prerequisite of poor prognosis of tumor development. The cellular localization of the ligand/receptor pair also requires consideration. The data concerning the expression of HMGB1 protein and its receptor RAGE in various tissues and tumor cells reflect the overall production of the proteins. However, they do not refer to their cellular localization and there is no direct evidence for the formation of a stable complex between them. In the present study, we investigated the subcellular distribution of HMGB1 and its receptor RAGE in various rat organs compared to Guerin ascites tumor cells. In the normal tissues the proteins exist in their soluble form, whereas in the tumor cells they are insoluble and membrane-bound. HMGB1 forms a stable complex with RAGE only in the protein extract derived from the cancer cells predominantly in the membrane fraction.
