Chemosensitization of T-47D breast carcinoma cells to TRAIL and Fas receptor-induced killing.
BACKGROUND
Although chemotherapeutic agents are known to sensitize some tumour types to killing through cell surface death receptors for Fas ligand and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), chemosensitization of breast carcinoma cells has not yet been explored.


METHODS
Mitochondrial thiazole tetrazolium assays were used to measure changes in MCF-7 and T-47D breast carcinoma cell viability. Semiquantitative RT-PCR was used to determine Fas and TRAIL receptor mRNA expression.


RESULTS
Treatment with suboptimal concentrations of etoposide or doxorubicin rendered T-47D cells sensitive to anti-Fas antibody or TRAIL, consistent with Fas and TRAIL-R1 mRNA expression by T-47D cells following drug treatment. In contrast, neither drug sensitized MCF-7 cells to TRAIL- or anti-Fas antibody, most likely due to diminished Fas and TRAIL-R1 expression following drug treatment.


CONCLUSIONS
These findings suggest that some breast carcinomas may respond favorably to a combination of chemotherapy and immunotherapy.
Morgan
Max
M
Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
Williams
Brent A
BA
Blay
Jonathan
J
Hoskin
David W
DW
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D005047:Etoposide; D004317:Doxorubicin