The cytotoxic effect of a combination of interferons (type I and II) and tumor necrosis factor (TNF), with an antiestrogenic drug, tamoxifen (TAM), was investigated in the estrogen receptor positive human breast carcinoma cell line, MCF-7.
Since overexpression of HER2/neu oncogenes in breast cancer cells is associated with resistance to the cytotoxic effect of tumor necrosis factor (TNF), we investigated whether this correlation also existed for ovarian cancer targets.
The expression of these transcripts in breast carcinoma tissue also was examined because breast cancer is a much more TNF-sensitive tumor than gastric cancer.
Since experimental studies have shown that tumour necrosis factor-alpha (TNF-alpha) has potent anti-tumour activity that can be potentiated with cytokines, we tested the efficacy of TNF-alpha with interferon-gamma (IFN-gamma) on different human breast cancer cell lines, particularly comparing hormone-dependent and -independent phenotypes.
Human breast cancer cells (MCF-7) overexpressing manganese-containing superoxide dismutase (MnSOD) by stable or transient transfection were challenged with the cytotoxicity of tumor necrosis factor alpha (TNF-alpha), hyperthermia, and a combination of both.
We found that TNF-alpha increased the secretion of TGF-beta in two established breast cancer cell lines (MCF-7 and ZR-75-1) but not in two immortalized human mammary epithelial cell lines (184B5 and MCF-10A).
Methyltransferase inhibitor S-adenosyl-L-homocysteine sensitizes human breast carcinoma MCF7 cells and related TNF-resistant derivatives to TNF-mediated cytotoxicity via the ceramide-independent pathway.
These data show that TNF-alpha-stimulated breast carcinoma cells express mediators that can both bind and activate eosinophils, suggesting a mechanism for eosinophil localization to breast carcinoma sites.
Cytotoxicity studies against log-phase human breast carcinoma cells (SKBR-3-HP) over-expressing HER2/neu demonstrate that the sFv23/TNF fusion construct was 1, 000-fold more active than free TNF.
The authors used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the hsp70-2 gene in 243 unrelated Tunisian patients with breast carcinoma and 174 healthy control subjects.
Several cytokines including members of the transforming growth factor-beta (TGF-beta) and tumor necrosis factor (TNF) families have been implicated in the homing mechanism of breast cancer metastasis.
Previous studies from our laboratory have indicated impaired production of TNF-alpha by monocytes as well as decreased expression of ICAM-1 on monocytes derived from patients with various stages of breast cancer.
We hypothesized that polymorphisms in IL-6 (-174 G>C) or TNF-alpha (G-238 or G-308) might be associated with prognosis in a subset of patients with high-risk breast cancer.
We demonstrated no association between the -308G>A polymorphism and the -238G>A polymorphism in the promoter region of TNF and susceptibility to breast cancer, in a large North European population.
Patient-control comparisons revealed a non-significant trend for association between the TNF-alpha-308 GG genotype and breast cancer compared to controls (79.7 vs. 68.2%, P = 0.03, Pc = 0.54).
In this study, we showed that tumor necrosis factor-alpha (TNF-alpha), TNF-related apoptosis-inducing ligand (TRAIL), and anti-Fas agonist antibody potentiated NaB-induced growth inhibition through synergistic induction of apoptosis in breast cancer cell lines (MCF-7, T47-D, and BT-20).
Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).
Recently, we showed the implication of the polymorphism in tumor necrosis factor-alpha (TNF-alpha) gene in the susceptibility and prognosis of breast carcinoma.