Mzf1 controls cell proliferation and tumorigenesis

被引:111
作者
Gaboli, M
Kotsi, PA
Gurrieri, C
Cattoretti, G
Ronchetti, S
Cordon-Cardo, C
Broxmeyer, HE
Hromas, R
Pandolfi, PP [1 ]
机构
[1] Cornell Univ, Mem Sloan Kettering Canc Ctr, Program Mol Biol, Sloan Kettering Div,Grad Sch Med Sci, New York, NY 10021 USA
[2] Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pathol, Sloan Kettering Div,Grad Sch Med Sci, New York, NY 10021 USA
[3] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA
[4] Indiana Univ, Med Ctr, Dept Med Hematol Oncol, Indianapolis, IN 46202 USA
[5] Indiana Univ, Med Ctr, Dept Immunol Microbiol, Indianapolis, IN 46202 USA
[6] Walther Canc Inst, Indianapolis, IN 46202 USA
关键词
MZF; hematopoiesis; tumorigenesis; knockout mice; myeloid progenitors;
D O I
10.1101/gad.902301
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MZF1 is a transcription factor belonging to the Kruppel family of zinc finger proteins, expressed in totipotent hemopoietic cells as well as in myeloid progenitors. Here we have inactivated Mzfi1 by gene targeting. Mzf1(-/-) mice develop lethal neoplasias characterized by the infiltration and complete disruption of the liver architecture by a monomorphic population of cells of myeloid origin reminiscent of human chloromas. Mzf1(-/-) inactivation results in a striking increase of the autonomous cell proliferation and of the ability of Mzf1(-/-) hemopoietic progenitors to sustain long-term hemopoiesis. These findings demonstrate that Mzf1 can act as a tumor/growth suppressor in the hemopoietic compartment.
引用
收藏
页码:1625 / 1630
页数:6
相关论文
共 23 条
[1]   Plzf regulates limb and axial skeletal patterning [J].
Barna, M ;
Hawe, N ;
Niswander, L ;
Pandolfi, PP .
NATURE GENETICS, 2000, 25 (02) :166-172
[2]   ANTISENSE OLIGONUCLEOTIDES FROM THE STAGE-SPECIFIC MYELOID ZINC FINGER GENE MZF-1 INHIBIT GRANULOPOIESIS INVITRO [J].
BAVISOTTO, L ;
KAUSHANSKY, K ;
LIN, N ;
HROMAS, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1991, 174 (05) :1097-1101
[3]  
CORDONCARDO C, 1994, AM J PATHOL, V144, P500
[4]   Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse [J].
Di Cristofano, A ;
De Acetis, M ;
Koff, A ;
Cordon-Cardo, C ;
Pandolfi, PP .
NATURE GENETICS, 2001, 27 (02) :222-224
[5]  
HARRISON TR, 1987, HARRISONS PRINCIPLES, P1545
[6]   Two critical hits for promyelocytic leukemia [J].
He, LZ ;
Bhaumik, M ;
Tribioli, C ;
Rego, EM ;
Ivins, S ;
Zelent, A ;
Pandolfi, PP .
MOLECULAR CELL, 2000, 6 (05) :1131-1141
[7]   Acute leukemia with promyelocytic features in PML/RAR alpha transgenic mice [J].
He, LZ ;
Tribioli, C ;
Rivi, R ;
Peruzzi, D ;
Pelicci, PG ;
Soares, V ;
Cattoretti, G ;
Pandolfi, PP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (10) :5302-5307
[8]   The location of MZF-1 at the telomere of human chromosome 19q makes it vulnerable to degeneration in aging cells [J].
Hoffman, SMG ;
Hromas, R ;
Amemiya, C ;
Mohrenweiser, HW .
LEUKEMIA RESEARCH, 1996, 20 (03) :281-283
[9]  
HROMAS R, 1991, J BIOL CHEM, V266, P14183
[10]  
Hromas R, 1996, CURR TOP MICROBIOL, V211, P159