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Soluble Fas/APO-1 in tumor cells: a potential regulator of apoptosis?
L B Owen-Schaub1, L S Angelo, R Radinsky
1Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
Fas/APO-1, a member of the NGF/TNF receptor superfamily expressed on the cell-surface of normal and malignant cells, is known to induce cell death by apoptosis. In the present study, we have investigated Fas/APO-1 gene defects in a human osteosarcoma cell line resistant to the apoptosis-inducing effects of anti-Fas. cDNA cloning and sequencing revealed that these cells contained both 'authentic' and mutant Fas/APO-1 containing a 63 base pair in-frame deletion spanning the transmembrane domain, designated DFas/APO-1. Direct evidence for the existence of a soluble Fas/APO-1 protein was obtained by immunoprecipitation and Western blotting. Taken together with prior studies demonstrating a role for Fas/APO-1 and Fas ligand, respectively, in tumor target cell killing by cytotoxic T-lymphocytes, production of soluble Fas/APO-1 might have significant implications in malignant disease pathogenesis.
Insights
Researchers found a mutant Fas/APO-1 gene in osteosarcoma cells resistant to apoptosis. This mutant Fas/APO-1 gene produces a soluble protein, potentially impacting cancer development.
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Fas/APO-1 receptor mediates apoptosis, a crucial process for cell death.
- Dysregulation of apoptosis is implicated in cancer development and treatment resistance.
Purpose of the Study:
- Investigate Fas/APO-1 gene defects in an osteosarcoma cell line resistant to anti-Fas induced apoptosis.
- Characterize the molecular basis of resistance to Fas/APO-1 mediated cell death.
Main Methods:
- cDNA cloning and sequencing to identify gene mutations.
- Immunoprecipitation and Western blotting to detect protein expression.
Main Results:
- Identified both authentic and a mutant Fas/APO-1 gene (DFas/APO-1) with a deletion in the transmembrane domain.
- Confirmed the presence of a soluble Fas/APO-1 protein in the resistant cells.
Conclusions:
- A soluble Fas/APO-1 protein, resulting from a gene defect, may contribute to resistance against apoptosis.
- The production of soluble Fas/APO-1 has potential implications in the pathogenesis of malignant diseases.