Evi-1 promotes para-aortic splanchnopleural hematopoiesis through up-regulation of GATA-2 and repression of TGF-β signaling

被引：35

作者：

Sato, Tomohiko ^{[1
]}

Goyama, Susumu ^{[1
]}

Nitta, Eriko ^{[1
]}

Takeshita, Masataka ^{[1
]}

Yoshimi, Mayumi ^{[1
]}

Nakagawa, Masahiro ^{[1
]}

Kawazu, Masahito ^{[1
]}

Ichikawa, Motoshi ^{[1
]}

Kurokawa, Mineo ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Bunkyo Ku, Tokyo 1138655, Japan

来源：

CANCER SCIENCE | 2008年 / 99卷 / 07期

关键词：

D O I：

10.1111/j.1349-7006.2008.00842.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Evi-1 is a zinc-finger transcriptional factor whose inappropriate expression leads to leukemic transformation in mice and humans. Recently, it has been shown that Evi-1 regulates proliferation of hematopoietic stem/progenitor cells at embryonic stage via GATA-2 up-regulation; however, detailed mechanisms underlying Evi-1-mediated early hematopoiesis are not fully understood. We therefore evaluated hematopoietic potential of Evi-1 mutants using a cultivation system of murine para-aortic splanchnopleural (P-Sp) regions, and found that both the first zinc finger domain and the acidic domain were required for Evi-1-mediated hematopoiesis. The hematopoietic potential of Evi-1 mutants was likely to be related to its ability to up-regulate GATA-2 expression. We also showed that the decreased colony forming capacity of Evi-1-deficient P-Sp cells was successfully recovered by inhibition of TGF-b signaling, using ALK5 inhibitor or retroviral transfer of dominant-negative-type Smad3. Our findings suggest that Evi-1 promotes hematopoietic stem/progenitor expansion at the embryonic stage through up-regulation of GATA-2 and repression of TGF-b signaling.

引用

页码：1407 / 1413

页数：7

共 35 条

[1] The role of EVI1 in normal and leukemic cells [J].