PRL-2 increases Epo and IL-3 responses in hematopoietic cells.
PRL-2 increases Epo and IL-3 responses in hematopoietic cells.
复制标题
DOI：
10.1016/j.bcmd.2010.02.013
复制
发表时间：
2010-04-15
影响因子：
2.3
通讯作者：
Yi, Taolin
中科院分区：
文献类型：
--
作者：
Akiyama, Shoko;Dhavan, Deepika;Yi, Taolin
双重特异性蛋白酪氨酸磷酸酶PRL-2在儿童急性髓性白血病（AML）中过度表达，并且位于人类染色体1 p35，该区域在恶性淋巴瘤和B细胞-慢性淋巴细胞白血病（B-CLL）中经常重排或扩增。PRL-2表达在造血系统恶性肿瘤中的意义知之甚少。在此，我们证明了PRL-2在小鼠前B细胞系BaF 3ER和小鼠骨髓细胞中的异位表达诱导了与恶性进展和转移相关的关键特征。PRL-2转染的Baf 3ER细胞对造血生长因子Epo或IL-3的生长反应增强，细胞周期缩短，细胞存活对Epo的需求降低（5倍），细胞迁移增加（3倍），细胞粘附减少（5倍），转化为与干细胞标志物Bmi-1表达增加（3倍）相关的未成熟细胞形态。当被转导到小鼠骨髓细胞中时，PRL-2增加Epo诱导的集落形成（4x）并产生更大的集落。这些观察结果提供了证据，提示PRL-2作为造血系统恶性肿瘤的致病分子，并表明其作为一种新的治疗靶点的潜力。
Dual specificity protein tyrosine phosphatase PRL-2 is over-expressed in pediatric acute myeloid leukemia (AML) and is located at human chromosome 1p35, a region often rearranged or amplified in malignant lymphoma and B cell-chronic lymphocytic leukemia (B-CLL). Little is known of the significance of PRL-2 expression in hematopoietic malignancies. Herein we demonstrated that ectopic expression of PRL-2 in murine pre-B cell line BaF3ER and mouse bone marrow cells induced key features associated with malignant progression and metastasis. PRL-2 transfected Baf3ER cells had augmented growth responses to hematopoietic growth factors Epo or IL-3 with shortened cell cycle, reduced requirement (5x) for Epo in cell survival, increased cell migration (3x), reduced cell adhesion (5x) and conversion to an immature cell morphology in association with increased expression (3x) of stem cell marker Bmi-1. When transduced into mouse bone marrow cells, PRL-2 increased Epo-induced colony formation (4x) and gave rise to larger colonies. These observations provide evidences implicating PRL-2 as a pathogenic molecule in hematopoietic malignancies and suggest its potential as a novel therapeutic target.
登录
查看更多内容
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
6.5
作者：
Lestou, VS;Gascoyne, RD;Horsman, DE
通讯作者：
Horsman, DE
影响因子：
16
作者：
Baudino, TA;Maclean, KH;Cleveland, JL
通讯作者：
Cleveland, JL
影响因子：
11.5
作者：
Kato, H;Semba, S;Yokozaki, H
通讯作者：
Yokozaki, H
影响因子：
56.9
作者：
Saha, S;Bardelli, A;Vogelstein, B
通讯作者：
Vogelstein, B