Abnormal activation of cytokine gene expression by intracisternal type A particle transposition: effects of mutations that result in autocrine growth stimulation and malignant transformation.
This review will focus on understanding the mechanisms resulting in the deregulated expression of cytokine genes that can lead to autocrine transformation. The murine genome contains over 2000 copies of intracisternal type A particles (IAPs), which under certain circumstances can transpose to different positions in the genome. When these transpositions affect the expression of a gene that can either positively or negatively regulate cell growth, a malignant or transformed cell may arise that has different growth characteristics than the parental cells. If this mutation confers a growth advantage to the cell, a tumor may develop. IAP transpositions have been frequently observed in hematopoietic cells, and they often affect cytokine gene expression. Genetic elements that possess similar transposable characteristics are also contained in the human genome. This review will discuss how IAP transpositions can result in the autocrine transformation of hematopoietic cells.
Wang
X Y
XY
Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, NC 27858, USA.
Steelman
L S
LS
McCubrey
J A
JA
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics*; D004251:DNA Transposable Elements; D003673:Defective Viruses / Q000235:genetics; D005786:Gene Expression Regulation; D007426:Genes, Intracisternal A-Particle; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D009857:Oncogenes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016185:Receptors, Interleukin-3 / Q000235:genetics; D012190:Retroviridae / Q000235:genetics
D016207:Cytokines; D004251:DNA Transposable Elements; D007377:Interleukin-3; D012333:RNA, Messenger; D016185:Receptors, Interleukin-3