Latexin is down-regulated in hematopoietic malignancies and restoration of expression inhibits lymphoma growth.
Latexin is down-regulated in hematopoietic malignancies and restoration of expression inhibits lymphoma growth.
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DOI：
10.1371/journal.pone.0044979
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liang Y
中科院分区：
文献类型：
--
作者：
Liu Y;Howard D;Rector K;Swiderski C;Brandon J;Schook L;Mehta J;Bryson JS;Bondada S;Liang Y
乳胶蛋白是小鼠造血干细胞数量的负调节因子。它在其他肿瘤中的表达失调使我们假设迟发蛋白在血液系统恶性肿瘤中可能具有肿瘤抑制特性。我们发现，latexin在多种白血病和淋巴瘤细胞系以及来自这些恶性肿瘤患者血液和骨髓的CD34+细胞中下调。5-aza-2 ' -脱氧胞嘧啶处理和亚硫酸盐测序显示肿瘤细胞中乳胶蛋白启动子的超甲基化。逆转录病毒介导的latexin过表达对A20小鼠淋巴瘤细胞体外生长抑制16倍，体内肿瘤体积抑制2倍。Latexin通过下调抗凋亡基因Bcl-2和Pim-2显著增加细胞凋亡，从而抑制淋巴瘤细胞的生长。潜在的分子机制介导的肿瘤抑制不是通过其典型的羧肽酶抑制剂活性。这些结果与latexin的肿瘤抑制作用一致，表明latexin在治疗恶性肿瘤方面可能具有临床疗效。
Latexin is a negative regulator of hematopoietic stem cell number in mice. Its dysregulated expression in other tumors led us to hypothesize that latexin may have tumor suppressor properties in hematological malignancies. We found that latexin was down-regulated in a variety of leukemia and lymphoma cell lines as well as in CD34+ cells from the blood and marrow of patients with these malignancies. 5-aza-2′-deoxycytodine treatment and bisulfite sequencing revealed hypermethylation of latexin promoter in tumor cells. Retrovirus-mediated latexin overexpression in A20 mouse lymphoma cells inhibited their in vitro growth by 16 fold and in vivo tumor volume by 2 fold. Latexin caused growth inhibition of lymphoma cells by significantly increasing apoptosis through the down-regulation of anti-apoptotic genes Bcl-2 and Pim-2. The molecular mechanism underlying latexin-mediated tumor inhibition was not through its canonical carboxypeptidase inhibitor activity. These results are consistent with a tumor suppressor role for latexin and suggest that latexin may have clinical efficacy in the treatment of malignancies.
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影响因子：
6.4
作者：
Kwong, J;Lo, KW;Huang, DP
通讯作者：
Huang, DP
影响因子：
64.8
作者：
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作者：
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DOI：
10.1196/annals.1395.005
发表时间：
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期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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