TIMP-1 EXPRESSION BY NORMAL LYMPHOCYTES AND IN LYMPHOID NEOPLASMS

我们研究了TIMP-1在一系列Burkitt细胞中的表达 台词。Burkitt淋巴瘤，常见于艾滋病患者，是一种侵袭性疾病 在免疫功能受损的宿主中没有有效治疗的肿瘤。 Northern印迹分析表明，TIMP-1在RNA水平表达 被研究的9条线路中有4条。来自非洲和美洲的细胞系 Burkitt氏细胞表达TIMP-1，t(8；14)和t(8；22)的Burkitt细胞也表达 易位。所有Burkitt细胞系的研究都是可演示的 TIMP-1RNA转录本分泌TIMP-1蛋白(经Western检测 杂交分析)进入培养基中。TIMP-1的表达不 与EBV感染、p53突变或myc表达水平相关 在这些队伍里。表达TIMP-1的细胞株具有较高的 TIMP-1阴性细胞与体外细胞增殖的比较 成绩单。我们正在提纯TIMP-1蛋白，并打算研究 TIMP-1对体外生长动力学的影响TIMP-1的表达 Burkitt细胞系在裸体体内的致瘤性和侵袭性也更强 老鼠模型。皮肤和神经的侵袭仅见于TIMP-1 表达的台词。这种咄咄逼人的行为可能是由于高增长 率，增强的侵犯性行为或两者的组合。我们是 目前正在研究四种细胞系(两种表达TIMP-1，两种 阴性)，以评估侵袭性行为。我们计划 含TIMP-1基因的逆转录病毒载体感染TIMP-1阴性细胞系 TIMP-1诱导TIMP-1表达以研究TIMP-1的作用 关于增长率和侵入性。 在所研究的四个Burkitt细胞系中，明胶酶B的活性可以 经同工酶谱证实，但未经Northern印迹分析证实。TIMP-1和 明胶酶B只在一个细胞系中共表达，而且非常低 注意到酶的表达。明胶酶B的剩余活性为 在TIMP-1阴性细胞系中呈阳性表达。明胶酶A的表达 在任何Burkitt细胞系中都没有观察到。如果TIMP-1在Burkitt‘s中起作用 淋巴瘤通过阻断明胶酶的活性，我们原本预计会 能够通过Northern印迹或酶谱显示明胶酶在 TIMP-1阳性细胞系。因为明胶酶可能出现在 这些细胞对细胞外基质的反应，我们正在研究 明胶酶A和明胶酶B在Burkitt细胞肿瘤中的表达 在裸鼠身上。

We have studied the expression of TIMP-1 in a series of Burkitt cell lines. Burkitt's lymphoma, common in AIDS patients, is an aggressive neoplasm without effective therapy in the immunocompromised host. Northern blot analysis reveals that TIMP-1 is expressed at the RNA level by 4 out of 9 lines studied. Cell lines from both African and American Burkitt's express TIMP-1, as do Burkitt cells with t(8;14) and t(8;22) translocations. All of the Burkitt cell lines studied with demonstrable TIMP-1 RNA transcripts secreted TIMP-1 protein (as determined by Western blot analysis) into the culture media. TIMP-1 expression does not correlate with EBV involvement, p53 mutations, or levels of myc expression in these lines. The cell lines that express TIMP-1 have a higher rate of cell proliferation in vitro compared to those negative for TIMP-1 transcripts. We are purifying TIMP-1 protein and intend to study the effect of TIMP-1 on growth kinetics in vitro. The TIMP-1 expressing Burkitt cell lines are also more tumorigenic and invasive in the nude mouse model. Invasion of skin and nerve is seen in only in TIMP-1 expressing lines. This aggressive behavior may be due to high growth rate, enhanced invasive behavior or a combination of the two. We are currently studying four cell lines (two expressing TIMP-1 and two negative) in invasion assays to assess invasive behavior. We plan to infect TIMP-1 negative cell lines with a retroviral construct containing TIMP-1 to cause TIMP-1 expression in order to study the effect of TIMP-1 on growth rate and invasiveness. In four of the Burkitt cell lines studied, Gelatinase B activity can be demonstrated by zymogram but not by Northern blot analysis. TIMP-1 and Gelatinase B coexpression is seen in only one cell line, with very low enzyme expression noted. The remainder of the Gelatinase B activity was demonstrated in TIMP-1 negative cell lines. Gelatinase A expression was not observed in any Burkitt cell lines. If TIMP-1 functions in Burkitt's lymphoma by blocking gelatinase activity, we would have expected to be able to demonstrate gelatinase expression by Northern blot or zymogram in the TIMP-1 positive cell lines. As gelatinase expression may occur in these cells in response to the extracellular matrix, we are studying the expression of Gelatinase A and Gelatinase B in Burkitt cell tumors grown in nude mice.