Macrophage-Colony-Stimulating Factor (CSF-1) Induces Proliferation Chemotaxis, and Reversible Monocytic Differentiation in Myeloid Progenitor Cells Transfected with the Human c-fms/CSF-1 Receptor cDNA

The c-fms protooncogene encodes the receptor for macrophage-colony-stimulating factor (CSF-1). Expression vectors containing either normal or oncogenic point-mutated human c-fms genes were transfected into interleukin 3 (IL-3)-dependent 32D cells in order to determine the effects of CSF-1 signaling...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1990-08, Vol.87 (15), p.5613-5617
Main Authors: Pierce, Jacalyn H., Di Marco, Eddi, Cox, George W., Lombardi, Daniela, Ruggiero, Marco, Varesio, Luigi, Wang, Ling Mei, Choudhury, G. Ghosh, Sakaguchi, Alan Y., Di Fiore, Pier Paolo, Aaronson, Stuart A.
Format: Article
Language:English
Subjects:
550201 - Biochemistry- Tracer Techniques
ANIMAL CELLS
Animals
ANTIGENS
BASIC BIOLOGICAL SCIENCES
BETA DECAY RADIOISOTOPES
Biological and medical sciences
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL DIFFERENTIATION
Cell Differentiation - drug effects
Cell Division - drug effects
Cell growth
Cell Line
Cell lines
Cell physiology
CELL PROLIFERATION
Cells
Cellular differentiation
Chemotaxis
Chemotaxis - drug effects
Colony-Stimulating Factors - metabolism
Colony-Stimulating Factors - pharmacology
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DNA
ELECTRON CAPTURE RADIOISOTOPES
Fundamental and applied biological sciences. Psychology
GENE REGULATION
GENES
GROWTH FACTORS
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - drug effects
Humans
INFLAMMATION
Interleukin-3 - pharmacology
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LEUKOCYTES
LYMPHOKINES
Macrophage Colony-Stimulating Factor
MACROPHAGES
MATERIALS
MEMBRANE PROTEINS
Mice
MITOGENS
Molecular and cellular biology
MONOCYTES
Monocytes - cytology
Monocytes - drug effects
Monocytes - physiology
MORPHOLOGICAL CHANGES
Mutation
NUCLEI
NUCLEIC ACIDS
ODD-EVEN NUCLEI
ONCOGENES
ORGANIC COMPOUNDS
PATHOLOGICAL CHANGES
PHAGOCYTES
Phenotypes
PROTEINS
Proto-Oncogene Proteins - drug effects
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
RADIOISOTOPES
RADIORECEPTOR ASSAY
Receptor, Macrophage Colony-Stimulating Factor
RECEPTORS
Receptors, Cell Surface - physiology
RECOMBINANT DNA
Responses to growth factors, tumor promotors, other factors
SOMATIC CELLS
Surface antigens
SYMPTOMS
TRACER TECHNIQUES
Transfection
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The c-fms protooncogene encodes the receptor for macrophage-colony-stimulating factor (CSF-1). Expression vectors containing either normal or oncogenic point-mutated human c-fms genes were transfected into interleukin 3 (IL-3)-dependent 32D cells in order to determine the effects of CSF-1 signaling in this murine clonal myeloid progenitor cell line. CSF-1 was shown to trigger proliferation in association with monocytic differentiation of the 32D-c-fms cells. Monocytic differentiation was reversible upon removal of CSF-1, implying that CSF-1 was required for maintenance of the monocyte phenotype but was not sufficient to induce an irrevocable commitment to differentiation. Human CSF-1 was also shown to be a potent chemoattractant for 32D-c-fms cells, suggesting that CSF-1 may serve to recruit monocytes from the circulation to tissue sites of inflammation or injury. Although c-fms did not release 32D cells from factor dependence, point-mutated c-fms [S301,F969] (Leu-301 → Ser, Tyr-969 → Phe) was able to abrogate their IL-3 requirement and induce tumorigenicity. IL-3-independent 32D-c-fms[S301,F969] cells also displayed a mature monocyte phenotype, implying that differentiation did not interfere with progression of these cells to the malignant state. All of these findings demonstrate that a single growth factor receptor can specifically couple with multiple intracellular signaling pathways and play a critical role in modulating cell proliferation, differentiation, and migration.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.87.15.5613