Platelet-derived growth factor receptor regulates myeloid and monocytic differentiation of HL-60 cells
Platelet-derived growth factor receptor regulates myeloid and monocytic differentiation of HL-60 cells
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DOI：
10.1158/0008-5472.can-07-0014
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发表时间：
2007-08-15
期刊：
影响因子：
11.2
通讯作者：
Yen, Andrew
中科院分区：
文献类型：
--
作者：
Reiterer, Gudrun;Yen, Andrew
在这里，我们发现血小板衍生生长因子受体（PDGFR）分别在维甲酸（RA）和维生素D3 (M)的作用下调节HL-60髓母细胞白血病细胞的髓系和单核细胞分化。RA和D3在整个分化过程中都降低了pdgfr - α和pdgfr - β的表达。当PDGFR抑制剂AG1296与RA或D3一起处理细胞时，终端分化的迹象，如诱导氧化代谢和细胞底物粘附增强。这些变化伴随着细胞外信号调节激酶1/2激活的增加。与RA或D3一起给药时，AG1296也导致分化标志物CD11b和CD66c的表达升高。有趣的是，其他标记物并没有遵循同样的模式。除RA或D3外，接受AG1296的细胞显示G(1)-G(0)阻滞和CD14， CD38和CD89表达降低。因此，我们提供的证据表明，某些组的分化标记可以增强，而其他组可以被PDGFR途径抑制。此外，我们发现RA和D3降低了钙水平，但在加用AG1296或D3时，钙水平升高，提示髓细胞或单核细胞分化过程中钙水平降低，钙水平升高会干扰某些分化标志物的表达。
Here, we show that the platelet-derived growth factor receptor (PDGFR) regulates myeloid and monocytic differentiation of HL-60 myeloblastic leukemia cells in response to retinoic acid (RA) and vitamin D3 (M), respectively. Both RA and D3 decreased the expression of PDGFR-alpha and PDGFR-beta through-out differentiation. When cells were treated with the PDGFR inhibitor AG1296 in addition to RA or D3, signs of terminal differentiation such as inducible oxidative metabolism an cell substrate adhesion were enhanced. These changes were accompanied by an increased extracellular signal-regulated kinase 1/2 activation. AG1296 also resulted in elevated expression of differentiation markers CD11b and CD66c when administered with RA or D3. Interestingly, other markers did not follow the same pattern. Cells receiving AG1296 in addition to RA or D3 showed decreased G(1)-G(0) arrest and CD14, CD38, and CD89 expression. We thus provide evidence that certain sets of differentiation markers can be enhanced, whereas others can be inhibited by the PDGFR pathway. In addition, we found calcium levels to be decreased by RA and D3 but increased when AG1296 was given in addition to or D3, suggesting that calcium levels decrease during myeloid or monocytic differentiation, and elevated calcium levels can disturb the expression of certain differentiation markers.