c-myb stimulates cell growth by regulation of insulin-like growth factor (IGF) and IGF-binding protein-3 in K562 leukemia cells

被引：17

作者：

Kim, Min-Sun ^{[1
]}

Kim, Sun-Young ^{[1
]}

Arunachalam, Sankaraganesh ^{[1
]}

Hwang, Pyoung-Han ^{[1
,2
]}

Yi, Ho-Keun ^{[3
]}

Nam, Sang-Yun ^{[4
]}

Lee, Dae-Yeol ^{[1
,2
]}

机构：

[1] Chonbuk Natl Univ, Dept Pediat, Sch Med, Jeonju 561712, South Korea

[2] Chonbuk Natl Univ, Res Inst Clin Med, Sch Med, Jeonju 561712, South Korea

[3] Chonbuk Natl Univ, Sch Dent, Dept Biochem, Jeonju 561712, South Korea

[4] Jeonju Univ, Sch Alternat Med & Hlth Sci, Dept Alternat Therapy, Jeonju 561712, South Korea

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 385卷 / 01期

关键词：

c-myb; DN-myb; IGFs; IGF-I receptor; IGFBP-3; Leukemia cells; BREAST-CANCER CELLS; FACTOR-I RECEPTOR; EXPRESSION; DIFFERENTIATION; INHIBITION; MECHANISM; APOPTOSIS; PATHWAY;

D O I：

10.1016/j.bbrc.2009.05.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

c-myb plays an important role in the regulation of cell growth and differentiation, and is highly expressed in immature hematopoietic cells. The human chronic myelogenous leukemia cell K562, highly expresses IGF-I, IGF-II, IGF-IR, and IGF-induced cellular proliferation is mediated by IGF-IR. To characterize the impact of c-myb on the IGF-IGFBP-3 axis in leukemia cells, we overexpressed c-myb using an adenovirus gene transfer system in K562 cells. The overexpression of c-myb induced cell proliferation, compared to control, and c-myb induced cell growth was inhibited by anti-IGF-IR antibodies. c-myb overexpression resulted in a significant increase in the expression of IGF-I, IGF-II, and IGF-IR, and a decrease in IGFBP-3 expression. By contrast, disruption of c-myb function by DN-myb overexpression resulted in significant reduction of IGF-I, IGF-II, IGF-IR, and elevation of IGFBP-3 expression. In addition, exogenous IGFBP-3 inhibited the proliferation of K562 cells, and c-myb induced cell growth was blocked by IGFBP-3 overexpression in a dose-dependent manner. The growth-promoting effects of c-myb were mediated through two major intracellular signaling pathways. Akt and Erk. Activation of Akt and Erk by c-myb was completely blocked by IGF-IR and IGFBP-3 antibodies. These findings suggest that c-myb stimulates cell growth, in part, by regulating expression of the components of IGF-IGFBP axis in K562 cells. In addition, disruption of c-myb function by DN-myb may provide a useful strategy for treatment of leukemia. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：38 / 43

页数：6

共 27 条

[1] Expression of insulin-like growth factors IGF-I and IGF-II, and their receptors during the growth and megakaryocytic differentiation of K562 cells [J].

Aro, ALA ;

Savikko, J ;

Pulkkinen, V ;

von Willebrand, E .

LEUKEMIA RESEARCH, 2002, 26 (09) :831-837

[2] RELATIONSHIP BETWEEN THE C-MYB LOCUS AND THE 6Q CHROMOSOMAL ABERRATION IN LEUKEMIAS AND LYMPHOMAS [J].

BARLETTA, C ;

PELICCI, PG ;

KENYON, LC ;

SMITH, SD ;

DALLAFAVERA, R .

SCIENCE, 1987, 235 (4792) :1064-1067

[3]

BAXTER RC, 1996, PROG GROWTH FACTOR R, V1, P619

[4] The phosphoinositide 3-kinase pathway [J].

Cantley, LC .

SCIENCE, 2002, 296 (5573) :1655-1657

[5] Insulin-like growth factor (IGF) binding protein-3 potentiation of IGF action is mediated through the phosphatidylinositol-3-kinase pathway and is associated with alteration in protein kinase B/AKT sensitivity [J].

Conover, CA ;

Bale, LK ;

Durham, SK ;

Powell, DR .

ENDOCRINOLOGY, 2000, 141 (09) :3098-3103

[6] THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR - STRUCTURE, LIGAND-BINDING MECHANISM AND SIGNAL-TRANSDUCTION [J].

DEMEYTS, P ;

WALLACH, B ;

CHRISTOFFERSEN, CT ;

URSO, B ;

GRONSKOV, K ;

LATUS, LJ ;

YAKUSHIJI, F ;

ILONDO, MM ;

SHYMKO, RM .

HORMONE RESEARCH, 1994, 42 (4-5) :152-169

[7] Adenoviral-mediated expression of human insulin-like growth factor-binding protein-3 [J].

Firth, SM ;

Ganeshprasad, U ;

Poronnik, P ;

Cook, DI ;

Baxter, RC .

PROTEIN EXPRESSION AND PURIFICATION, 1999, 16 (01) :202-211

[8] G1/S TRANSITION IN NORMAL HUMAN LYMPHOCYTES-T REQUIRES THE NUCLEAR-PROTEIN ENCODED BY C-MYB [J].

GEWIRTZ, AM ;

ANFOSSI, G ;

VENTURELLI, D ;

VALPREDA, S ;

SIMS, R ;

CALABRETTA, B .

SCIENCE, 1989, 245 (4914) :180-183

[9]

GJERSET RA, 1990, J IMMUNOL, V145, P3467

[10]

Gucev ZS, 1996, CANCER RES, V56, P1545

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