Aberrant expression of the myeloid zinc finger gene, MZF-1, is oncogenic.
The zinc finger gene MZF-1 is preferentially expressed in primitive hematopoietic cells and plays an important role in regulating myelopoiesis. Regulators of development are potential targets for neoplastic transformation. This study investigated whether unregulated expression of MZF-1 could function as an oncogene. Retroviral transduction and subsequent overexpression of MZF-1 resulted in loss of contact inhibition, loss of substrate dependence, and more rapid cell cycling in NIH 3T3 cells. The MZF-1-transformed 3T3 cells formed aggressive tumors in athymic mice. Disruption of the tight lineage- and stage-specific regulation of MZF-1 can result in neoplastic transformation of embryonic fibroblasts. Therefore, MZF-1 represents a novel oncogene.
Hromas
R
R
Department of Medicine, Walther Oncology Center, Indiana University Medical Center, Indianapolis 46202, USA.
Morris
J
J
Cornetta
K
K
Berebitsky
D
D
Davidson
A
A
Sha
M
M
Sledge
G
G
Rauscher
F
F
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics; D010455:Peptides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014161:Transduction, Genetic; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C490095:Mzf1 protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D014157:Transcription Factors