Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis
Leukemic transformation of normal murine erythroid progenitors: v- and c-ErbB act through signaling pathways activated by the EpoR and c-Kit in stress erythropoiesis
复制标题
正常小鼠红系祖细胞的白血病转化：v-和 c-ErbB 通过 EpoR 和 c-Kit 在应激性红细胞生成中激活的信号通路发挥作用
作者：
M. Lindern;E. Deiner;H. Dolznig;M. P. Amelsvoort;M. Hayman;E. Mullner;H. Beug
通过促红细胞生成素（Epo）、干细胞因子（SCF）和糖皮质激素的协同作用，可以扩增原代红系祖细胞。虽然Epo通常是红细胞生成所需的，但糖皮质激素和SCF主要有助于缺氧小鼠的应激红细胞生成。正常红系祖细胞在应激条件下经历扩增的这种能力是由携带致癌基因v-ErbB和v-ErbA的禽成红细胞增多症病毒（AEV）靶向的。我们研究了应激条件下和白血病转化中祖细胞扩增所需的信号通路。红系祖细胞的永生株，能够在适当的条件下进行正常的终末分化，从p53−/−小鼠的胎肝中建立。EGF受体（HER-1/c-ErbB）或其突变的致癌版本（v-ErbB）在这些细胞中的表达和激活消除了这些祖细胞扩增中对Epo和SCF的需求，并阻断了终末分化。在抑制ErbB功能后，发生向红细胞的分化。对于更新诱导重要的信号转导分子，即Stat 5-和磷酸肌醇3-激酶（PI 3 K），被EpoR/c-Kit和v/c-ErbB两者利用。然而，虽然v-ErbB转化细胞和正常祖细胞依赖于PI 3 K信号转导进行更新，但c-ErbB也通过PI 3 K非依赖性机制诱导祖细胞扩增。
Primary erythroid progenitors can be expanded by the synergistic action of erythropoietin (Epo), stem cell factor (SCF) and glucocorticoids. While Epo is required for erythropoiesis in general, glucocorticoids and SCF mainly contribute to stress erythropoiesis in hypoxic mice. This ability of normal erythroid progenitors to undergo expansion under stress conditions is targeted by the avian erythroblastosis virus (AEV), harboring the oncogenes v-ErbB and v-ErbA. We investigated the signaling pathways required for progenitor expansion under stress conditions and in leukemic transformation. Immortal strains of erythroid progenitors, able to undergo normal, terminal differentiation under appropriate conditions, were established from fetal livers of p53−/− mice. Expression and activation of the EGF-receptor (HER-1/c-ErbB) or its mutated oncogenic version (v-ErbB) in these cells abrogated the requirement for Epo and SCF in expansion of these progenitors and blocked terminal differentiation. Upon inhibition of ErbB function, differentiation into erythrocytes occurred. Signal transducing molecules important for renewal induction, i.e. Stat5- and phosphoinositide 3-kinase (PI3K), are utilized by both EpoR/c-Kit and v/c-ErbB. However, while v-ErbB transformed cells and normal progenitors depended on PI3K signaling for renewal, c-ErbB also induces progenitor expansion by PI3K-independent mechanisms.
干细胞因子与其受体 c-kit 的相互作用介导小鼠脾脏中造血细胞的沉积和急性扩张。
影响因子：
20.3
作者：
Broudy,VC;Lin,NL;Priestley,GV;Nocka,K;Wolf,NS
通讯作者：
Wolf,NS
DOI：
10.1042/bj3500001
发表时间：
2000-08
期刊：
The Biochemical journal
影响因子：
--
作者：
M. Lemmon;K. Ferguson
通讯作者：
M. Lemmon;K. Ferguson
小鼠乳腺上皮细胞中的 p53 突变：培养物的不稳定性以及体外与体内突变选择的不一致。
DOI：
--
发表时间：
1993
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
Ozbun,MA;Medina,D;Butel,JS
通讯作者：
Butel,JS