Peripheral T lymphocytes from women with breast cancer exhibit abnormal protein expression of several signaling molecules
- 25 September 1998
- journal article
- Published by Wiley in International Journal of Cancer
Abstract
We examined signaling molecules of peripheral blood T lymphocytes obtained from women with breast cancer. In 6 of 14 patients, T lymphocytes displayed an impaired ability to translocate NFêB p65 (Rel-A) following activation by anti-CD3 and IL-2. This observation was made despite normal cytoplasmic levels of the Rel-A protein. We also detected abnormally low levels of the signaling molecules T-cell receptor (TCR)-zeta, ZAP-70 and p56lck in 4 of 14 breast cancer patients, i.e., defects in T-cell signaling molecules. T lymphocytes from 6 of the 14 patients also exhibited an increased expression of the dual specificity phosphatase, map kinase phosphatase-1 (MKP-1). MKP-1 inactivates MAP kinase and therefore may interfere with the activation of c-jun and c-fos. Abnormalities of I or more signaling molecules were found in 9 of 14 patients; however, only 3 patients had T cells that exhibited all 5 defects. Our data have implications for the detection of potentially dysfunctional T cells in patients with cancer. For example, the analysis of only 1 signaling molecule may allow patients with significant defects in T-cell signaling to go unnoticed. Finally, despite impaired Rel-A translocation, T cells were capable of transcribing IL-2. Impairments in the translocation of Rel-B and c-Rel further suggest that the NFKB family members Rel-A, Rel-B and c-Rel are not required for the transcription of IL-2 in the peripheral T lymphocytes of patients with breast cancer.Keywords
This publication has 15 references indexed in Scilit:
- Alterations in T cells of cancer-bearers: whence specificity?Immunology Today, 1996
- Hydrogen peroxide secreted by tumor‐derived macrophages down‐modulates signal‐transducing zeta molecules and inhibits tumor‐specific T cell‐and natural killer cell‐mediated cytotoxicityEuropean Journal of Immunology, 1996
- Variable expression of CD3‐ζ chain in tumor‐infiltrating lymphocytes (TIL) derived from renal‐cell carcinoma: Relationship with til phenotype and functionInternational Journal of Cancer, 1995
- T cells from late tumor-bearing mice express normal levels of p56lck, p59fyn, ZAP-70, and CD3 zeta despite suppressed cytolytic activity.The Journal of Experimental Medicine, 1995
- Alterations in the signal‐transducing molecules of T cells and nk cells in colorectal tumor‐infiltrating, gut mucosal and peripheral lymphocytes: Correlation with the stage of the diseaseInternational Journal of Cancer, 1995
- Activated macrophages induce structural abnormalities of the T cell receptor-CD3 complex.The Journal of Experimental Medicine, 1995
- JNK is involved in signal integration during costimulation of T lymphocytesCell, 1994
- Function and Activation of NF-kappaB in the Immune SystemAnnual Review of Immunology, 1994
- Signal transduction by lymphocyte antigen receptorsCell, 1994
- Inability of CD8α′polypeptides to associate with p56lck correlates with impaired function in vitro and lack of expression in vivoNature, 1989