Basic fibroblast growth factor modulates the expression of glycophorin A and c-kit and inhibits erythroid differentiation in K562 cells.
Basic fibroblast growth factor (bFGF) is produced by bone marrow stromal cells as well as by normal and leukemic hematopoietic cells. In this study, we examine the direct effects of bFGF on erythroid differentiation in K562 cells in order to determine whether bFGF can promote the expression of a primitive phenotype. Low levels of bFGF inhibited erythroid differentiation as evidenced by decreased expression of glycophorin A and increased expression of c-kit. bFGF also increased both the numbers and the sizes of colonies of K562 cells in soft agar assays. The addition of TGF-beta to these cells induced erythroid differentiation which resulted in an increase in glycophorin A and a decrease in c-kit. The simultaneous addition of bFGF and TGF-beta to K562 cells prevented both the TGF-beta-mediated increase in glycophorin A expression and the decrease in c-kit expression associated with erythroid differentiation. bFGF antagonised the TGF-beta-mediated promotion of erythroid differentiation in K562 cells in a dose dependent manner and these two cytokines counteracted each other on an approximately molar basis. These results indicate that bFGF alone increases expression of c-kit and promotes a primitive phenotype in K562 cells. In addition, bFGF counteracts the effects of differentiation-inducing cytokines, such as TGF-beta, on hematopoietic cells. It is therefore possible that enhanced production of bFGF by leukemic cells could contribute to their neoplastic phenotype by opposing the effects of negative regulators or cytokines that induce differentiation.
Burger
Patricia E
PE
Department of Immunology, University of Cape Town, Cape Town, South Africa.
Lukey
Pauline T
PT
Coetzee
Sandra
S
Wilson
E Lynette
EL
D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006021:Glycophorins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology
D006021:Glycophorins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D019009:Proto-Oncogene Proteins c-kit