Lipocalin 2 is required for BCR-ABL-induced tumorigenesis.
Lipocalin 2 is required for BCR-ABL-induced tumorigenesis.
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DOI：
10.1038/onc.2008.209
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发表时间：
2008-10-16
期刊：
影响因子：
8
通讯作者：
Arlinghaus, R.
中科院分区：
文献类型：
--
作者：
Leng, X.;Lin, H.;Ding, T.;Wang, Y.;Wu, Y.;Klumpp, S.;Sun, T.;Zhou, Y.;Monaco, P.;Belmont, J.;Aderem, A.;Akira, S.;Strong, R.;Arlinghaus, R.
我们以前的研究表明，通过反义或siRNA方法降低Lipocalin 2(小鼠24p3)的表达，可以显著减少NOD/SCID小鼠骨髓和脾中bcr-abl+小鼠髓系32D的过度生长。在本研究中，我们使用小鼠骨髓移植模型，进一步探讨24p3在bcr-abl诱导的白血病中的作用。与我们以前的发现一致的是，当使用未照射的小鼠作为受者时，表达bcr-abl但缺乏24p3的供者骨髓细胞在75天后没有引起白血病或任何疾病，而所有接受野生型bcr-abl供体细胞的小鼠都死于CML样病。BCR-ABL+人CML细胞系K562(C5)的琼脂克隆分泌较高水平的Lipocalin 2(人NGAL)诱导小鼠脾和骨髓的造血抑制，导致早期死亡，而亲本K562或K562克隆(C6)表达较低的NGAL。与K562细胞相比，在K562细胞中过表达NGAL导致接种小鼠脾细胞出现更高的凋亡率和萎缩表型。与健康人相比，白血病小鼠和CML患者的血浆Lipocalin 2水平均升高。此外，我们发现，表达bcr-abl的野生型小鼠骨髓细胞的原代稳定细胞系在裸鼠体内引起实体瘤，而来自24p3基因缺失小鼠的类似的bcr-abl+细胞系不会引起实体瘤。这些发现表明，Lipocalin 2至少有两个与肿瘤发生有关的功能，一个是诱导正常造血细胞的凋亡，另一个是白血病细胞的组织侵袭。
Our previous studies indicate that reduction of lipocalin 2 (mouse 24p3) expression by either anti-sense or siRNA approaches strongly reduces the overgrowth of BCR-ABL + mouse myeloid 32D in marrow and spleen of NOD/SCID mice. In this study, we used the mouse bone marrow transplant model to further explore the role of 24p3 in BCR-ABL-induced leukemia. Consistent with our previous findings, when using non-irradiated mice as recipient, donor marrow cells expressing BCR-ABL but lacking 24p3 did not cause leukemia or any disease after 75 days, whereas all mice receiving wild type BCR-ABL donor cells died with CML-like disease. An agar clone of the BCR-ABL + human CML cell line K562 (C5) that secretes relatively high levels of lipocalin 2 (human NGAL) induced suppression of hematopoiesis in spleen and marrow of mice, leading to early death in contrast to parental K562 or K562 clone (C6) expressing low amounts of NGAL. Compared withK562 cells, overexpressing NGAL in K562 led to a higher apoptosis rate and an atrophy phenotype in the spleen of the inoculated mice. Plasma from both leukemic mice and CML patients showed elevated lipocalin 2 levels compared with healthy individuals. Moreover, we found that a primary stable cell line from wild-type mouse marrow cells expressing BCR-ABL caused solid tumors in nude mice whereas a similar BCR-ABL + cell line from 24p3 null mice did not. These findings demonstrate that lipocalin 2 has at least two functions related to tumorigenesis, one involving apoptosis induction of normal hematopoietic cells and the other being tissue invasion by leukemia cells.
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影响因子：
4.8
作者：
Yan, L;Borregaard, N;Moses, MA
通讯作者：
Moses, MA
影响因子：
8
作者：
Lin, F;Monaco, G;Arlinghaus, RB
通讯作者：
Arlinghaus, RB
影响因子：
64.5
作者：
GROFFEN, J;STEPHENSON, JR;GROSVELD, G
通讯作者：
GROSVELD, G
DOI：
10.1073/pnas.0510847103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Berger, T;Togawa, A;Mak, TW
通讯作者：
Mak, TW
影响因子：
16
作者：
Goetz, DH;Holmes, MA;Strong, RK
通讯作者：
Strong, RK