Downregulation of c-kit (Stem Cell Factor Receptor) in Transformed Hematopoietic Precursor Cells by Stroma Cells
| Autor: | Ulla Bergholz, Martina Bögel, Christine Laker, Christoph Heberlein, Wolfram Ostertag, Dorothee von Laer, Karl Klingler, Leonie K. Ashman, Jutta Friel |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
medicine.medical_specialty
Transcription Genetic Receptor expression Molecular Sequence Data Immunology Down-Regulation Stem cell factor Biology Polymerase Chain Reaction Biochemistry Cell Line Mice Stroma Downregulation and upregulation Cell–cell interaction Internal medicine medicine Animals Humans RNA Messenger Progenitor cell Stem Cell Factor Base Sequence Granulocyte-Macrophage Colony-Stimulating Factor Cell Biology Hematology Blotting Northern Hematopoietic Stem Cells Recombinant Proteins Cell biology Proto-Oncogene Proteins c-kit Haematopoiesis Endocrinology Gene Expression Regulation Interleukin-3 Stromal Cells Stem cell Cell Division |
| Zdroj: | Blood. 93:554-563 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v93.2.554 |
| Popis: | We show a dramatic downregulation of the stem cell factor (SCF) receptor in different hematopoietic cell lines by murine stroma. Growth of the human erythroid/macrophage progenitor cell line TF-1 is dependent on granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). However, TF-1 cells clone and proliferate equally well on stroma. Independent stroma-dependent TF-1 clones (TF-1S) were generated on MS-5 stroma. Growth of TF-1S and TF-1 cells on stroma still requires interaction between c-kit (SCF receptor) and its ligand SCF, because antibodies against c-kit inhibit growth to less than 2%. Surprisingly, c-kit receptor expression (RNA and protein) was downregulated by 2 to 3 orders of magnitude in TF-1S and TF-1 cells grown on stroma. This stroma-dependent regulation of the kit receptor in TF-1 was also observed on exposure to kit ligand-negative stroma, thus indicating the need for heterologous receptor ligand interaction. Removal of stroma induced upregulation by 2 to 4 orders of magnitude. Downregulation and upregulation of c-kit expression could also be shown for the megakaryocytic progenitor cell line M-07e and was comparable to that of TF-1, indicating that stroma-dependent regulation of c-kit is a general mechanism. Downregulation may be an economic way to compensate for the increased sensitivity of the c-kit/ligand interaction on stroma. The stroma-dependent c-kit regulation most likely occurs at the transcriptional level, because mechanisms, such as splicing, attenuation, differential promoter usage, or mRNA stability, could be excluded. |
| Databáze: | OpenAIRE |
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