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Paclitaxel Treatment of Breast Cancer Cell Lines Modulates Fas/Fas Ligand Expression and Induces Apoptosis Which Can Be Inhibited through the CD40 Receptor
- Source :
- Oncology. 66:101-111
- Publication Year :
- 2004
- Publisher :
- S. Karger AG, 2004.
-
Abstract
- Objective: Cytotoxic chemotherapy of advanced breast cancer is frequently complicated by drug resistance. Our goal was to define the role of the apoptosis-regulating receptors Fas (CD95) and CD40 in the chemosensitivity of breast cancer. Methods: The sensitivity of four breast cancer cell lines to paclitaxel and mitoxantrone was evaluated using an ATP-based cell viability assay. After verification of apoptosis by annexin V staining and TUNEL assay, cell lines were characterized regarding their constitutive expression of both surface and soluble (s)Fas (CD95) and Fas ligand (Fas-L). The role of the Fas/Fas-L system and different caspases was assessed by blocking drug-mediated apoptosis with specific antibodies. Finally, the paclitaxel sensitivity of the CD40-negative cell line KS was compared to that of its CD40-positive transfectant KS-CD40. Results and Conclusion: While the cytotoxic effect of mitoxantrone did not correlate with Fas expression, the results presented here suggest some involvement of the Fas/Fas-L system in paclitaxel-induced apoptosis. Cell lines with constitutive expression of Fas/sFas demonstrated a higher sensitivity to paclitaxel than Fas-negative cells. Incubation with paclitaxel led to a measurable downregulation of the expression of both soluble and surface Fas receptor in these cells. Interestingly, stimulation of the CD40 receptor inhibited paclitaxel-induced apoptosis in the transfected cell line KS-CD40, suggesting a role of this receptor in the modulation of chemosensitivity.
- Subjects :
- Cancer Research
medicine.medical_specialty
Fas Ligand Protein
Paclitaxel
CD40 Ligand
Apoptosis
Breast Neoplasms
Enzyme-Linked Immunosorbent Assay
Biology
Transfection
Fas ligand
chemistry.chemical_compound
Annexin
Cell Line, Tumor
Internal medicine
medicine
Humans
Cytotoxic T cell
fas Receptor
Viability assay
Receptor
Membrane Glycoproteins
General Medicine
Flow Cytometry
Fas receptor
Antineoplastic Agents, Phytogenic
Gene Expression Regulation, Neoplastic
Endocrinology
Oncology
chemistry
Cancer research
Female
Subjects
Details
- ISSN :
- 14230232 and 00302414
- Volume :
- 66
- Database :
- OpenAIRE
- Journal :
- Oncology
- Accession number :
- edsair.doi.dedup.....31b3afa956f7ff6b0a1a6d5025cdb340