THE CYTOKINE RECEPTOR REPERTOIRE SPECIFIES AUTOCRINE GROWTH-FACTOR PRODUCTION IN FACTOR-DEPENDENT CELLS
- Author(s)
- Rasko, JEJ; Metcalf, D; Gough, NM; Begley, CG;
- Details
- Publication Year 1995-05,Volume 23,Issue #5,Page 453-460
- Journal Title
- EXPERIMENTAL HEMATOLOGY
- Publication Type
- Journal Article
- Abstract
- Mechanisms of helper virus-induced growth factor-independence were examined in FDC-P1 cells and FDC-P1 cells expressing the erythropoietin receptor (FDER cells). Retroviral mutagenesis of FDC-P1 cells led to factor-independent (FI) colonies from which cell lines could readily be established; whereas control cells exhibited at least 20 to 40-fold lower rates of factor-independence. From 44 independent experiments using either FDC-P1 or FDER cells, 205 autonomous cell lines were obtained. Sixteen colonies displayed a novel (''satellite-inducing'') appearance in agar and produced up to 4.1x10(5) U/mL granulocyte-macrophage colony-stimulating factor (GM-CSF) (some with altered GM-CSF transcript sizes) and/or interleukin-3 (IL-3). Retroviral mutagenesis of FDER cells increased the repertoire of autocrine growth factors now responsible for stimulating autocrine proliferation: 3% of FI cell lines produced erythropoietin (Epo) (0.5 U/mL). Unexpectedly, in every autonomous FDC-P1 cell line, reverse transcriptase-PCR demonstrated expression of a growth factor normally required for proliferation Thus, a profound selection for cells able to produce growth factors as the mechanism for achieving autonomous proliferation was documented. The ectopic expression of a receptor lacking a cognate ligand (''orphan'') followed by retroviral mutagenesis and selection for autocrine mutants may offer an effective method for identifying new ligands.
- Publisher
- CARDEN JENNINGS PUBL COLTD
- Keywords
- COLONY-STIMULATING FACTOR; LEUKEMIA-INHIBITORY FACTOR; FACTOR GENE ACTIVATION; CSF TRANSGENIC MICE; HEMATOPOIETIC-CELLS; GM-CSF; INTERLEUKIN-3 GENE; AUTONOMOUS GROWTH; MOLECULAR-CLONING; MYELOID-LEUKEMIA
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Creation Date: 1995-05-01 12:00:00