Enhanced expression of HLA-A,B,C and inducibility of TAP-1, TAP-2, and HLA-A,B,C by interferon-gamma in a multidrug-resistant small cell lung cancer line
| Autor: | B, Fisk, C G, Ioannides, S, Aggarwal, J T, Wharton, C A, O'Brian, N, Restifo, B S, Glisson |
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| Rok vydání: | 1994 |
| Předmět: |
Cytotoxicity
Immunologic Ovarian Neoplasms Lung Neoplasms Base Sequence Molecular Sequence Data Drug Resistance Gene Expression Breast Neoplasms Recombinant Proteins Interferon-gamma ATP Binding Cassette Transporter Subfamily B Member 3 HLA Antigens Tumor Cells Cultured Humans ATP-Binding Cassette Transporters Female ATP Binding Cassette Transporter Subfamily B Member 2 Carcinoma Small Cell Carrier Proteins Killer Cells Lymphokine-Activated DNA Primers Etoposide |
| Zdroj: | Lymphokine and cytokine research. 13(2) |
| ISSN: | 1056-5477 |
| Popis: | Recent evidence suggests that deficient HLA Class I expression in SCLC lines may be due, in part, to down-regulation of TAP-1 and TAP-2 expression, and, thus, deficient antigen processing. Given the capability of the multidrug transporter mediating MDR, P-gp, to transport peptides, we hypothesized that P-gp may substitute for TAP-1/TAP-2 and enhance antigen processing in SCLC. To investigate this, we studied the H69 line (parent SCLC) and VPR-2 (MDR subline selected in etoposide, P-gp +). HLA-A,B,C expression was significantly increased in VPR-2 cells relative to H69, and was much more inducible with IFN-gamma. TAP-1 and TAP-2 were expressed at low levels in both lines. Differential induction of TAP-1 expression with IFN-gamma exposure was observed, with a dramatic increase in VPR-2 cells, and no change in H69. TAP-2 expression was enhanced in both lines with IFN-gamma, but to a greater degree in VPR-2. VPR-2 cells were resistant to LAK killing relative to H69, and were minimally sensitized with IFN-gamma. In contrast, IFN-gamma enhanced susceptibility of H69 to LAK killing 3-fold. The direct correlation between enhancement of HLA-A,B,C expression by IFN-gamma and the differential inducibility of TAP-1 and TAP-2 expression in P-gp-SCLC lines is novel. Relative LAK sensitivity of H69 and its increase by IFN-gamma may have clinical implications. |
| Databáze: | OpenAIRE |
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