FasL: Fas ratio - a prognostic factor in breast carcinomas

Department of Obstetrics and Gynecology, University of Rostock, Germany.
Cancer Research (Impact Factor: 9.33). 02/2000; 60(4):822-8.
Source: PubMed


Programmed cell death (apoptosis) is primarily mediated by Fas ligand (FasL; CD95L) and the Fas receptor (Fas; CD95). In this study, FasL was detected by immunohistochemical analysis in 85% of breast carcinomas and 14% of fibroadenomas randomly chosen, indicating that high expression of FasL might play a role in tumor pathology. FasL and Fas levels as well as FasL:Fas ratios were further ascertained in 215 human breast tumors, including 199 invasive ductal carcinomas, by real-time quantitative reverse transcription-PCR and compared with expression levels and ratios found in 25 normal human tissues, in 37 fibroadenomas, and in 5 normal breast tissues. Among breast carcinomas, high FasL mRNA expression seems to be positively correlated with histological grading (n = 212; P<0.0001). A ratio of FasL:Fas mRNA transcripts >1 is found to be significantly associated with decreased patient's disease-free survival (n = 211; P<0.03) and increased mortality (n = 211; P = 0.19). A FasL:Fas ratio >1 is related to tumor progression scored by histological grading (n = 212; P<0.02). The selection process leading to highly aggressive breast tumor variants might be enhanced by FasL-mediated tumor fratricide, eventually a possible target for novel therapeutic strategies.

Download full-text


Available from: Hans-Jürgen Thiesen, Jan 24, 2014
  • Source
    • "Breast cancer (BC) is the most common type of cancer in women and is a leading cause of cancer-related deaths worldwide. Adjuvant chemotherapy is the standard systemic treatment for breast cancer patients after surgical removal of tumor [1]. The anticancer drugs used in chemotherapy for tumors kill cancer cells predominantly by triggering apoptosis in them [2]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Anticancer agents used in chemotherapy for tumors induce apoptosis in malignant cells. Soluble Fas ligand, granzyme B and cytochrome c are key elements in the process of apoptosis. The objective of this preliminary study was to evaluate the changes in the serum concentrations of these parameters in breast cancer patients undergoing adjuvant chemotherapy. Materials and methods: Sixty patients with histopathologically proven breast cancer were included in the present study. The blood samples were taken after surgery before chemotherapy and after 3weeks of administration of the first cycle of chemotherapy. Thirty healthy female controls were selected for comparison. Soluble FasL, granzyme B and cytochrome c were estimated from serum by ELISA. Results: Significantly increased concentrations of soluble FasL, granzyme B and cytochrome c were found in stage II and stage III of breast cancer patients after chemotherapy compared with concentrations before chemotherapy (P<0.0001). A significant positive correlation was found between soluble FasL and cytochrome c as well as between granzyme B and cytochrome c in breast cancer patients after chemotherapy. Conclusion: Serum concentrations of apoptotic markers such as soluble FasL, granzyme B and cytochrome c were increased after administration of the first cycle of chemotherapeutic drugs. The measurement of these circulating apoptotic markers may help clinicians in evaluating treatment efficacy in breast cancer.
    Clinica Chimica Acta 08/2014; 438. DOI:10.1016/j.cca.2014.08.012 · 2.82 Impact Factor
  • Source
    • "Resistance to apoptosis and alterations in Fas signalling were initially observed in breast carcinoma cell lines (15). Several further studies on breast cancer patients indicated that the Fas/FasL status may have a significant impact on patient survival (16–19). These results, together with the evidence obtained during experiments on other solid malignancies (20–26), suggest that the tumour levels of Fas/FasL possibly influence the prognosis of oncology patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last century there has been great progress in the treatment of breast cancer by improving drug and radiation therapy as well as surgical techniques. Despite this development, breast cancer remains a major cause of death among women in Europe and the US. The cause of breast cancer at the cellular level is still not fully understood. In the present study, we investigated the expression of the Lifeguard β-isoform in breast cancer tissues. In contrast to Lifeguard, the β‑isoform has one transmembrane domain less, which is the last of seven (99 bp), and due to this we suspect that the Lifeguard β-isoform exhibits a different function. We determined the expression and function of the β-isoform of Lifeguard in breast cancer cell lines (MCF-7 and MDA-MB-231), a human breast epithelial cell line (MCF10A) and in breast tumour tissue sections. Western blotting, PCR arrays and immunofluorescence were used to investigate the expression of Lifeguard and its β-isoform. Moreover, we investigated the ability of Lifeguard β-isoform expression to inhibit apoptosis induced by Fas. Our results indicated that Lifeguard β-isoform is strongly expressed in breast tumour tissues. More notably, we demonstrated that Fas sensitivity was reduced in the MCF10A breast cells expressing the Lifeguard β-isoform. Taken together, our findings indicate the role of the Lifeguard β-isoform as an anti‑apoptotic protein and provide further evidence of the potential of the Lifeguard β-isoform as a target for the development of novel therapeutic strategies.
    Oncology Reports 07/2014; 32(4). DOI:10.3892/or.2014.3363 · 2.30 Impact Factor
  • Source
    • "Resistance to apoptosis and alterations in Fas signaling were observed first in breast carcinoma cell lines [18]. Several further studies on breast cancer patients indicated that Fas/FasL status may have a significant impact on patient survival [12, 14, 19, 20]. Their results, together with the evidence obtained during experiments on other solid malignancies [21–27], suggest that the tumor levels of Fas/FasL possibly will influence the prognosis of oncological patients. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Fas and its ligand (FasL) are known to play a crucial role in the genetically controlled mechanism of cell death, and their deregulation in cancer cells is involved in the immune escape of the tumor. The aim of this review is to analyze the current knowledge on the prognostic value of Fas/FasL in breast cancer patients. Both the results of other authors and our own experiences indicate that the lack of Fas ligand, and particularly Fas, is related to a significantly worse prognosis. It probably results from the resistance of Fas-deficient breast tumors to the mechanisms of apoptosis. On the other hand, some results suggest that the Fas/FasL-dependent mechanisms of tumor spread may be different for various target tissues. The expression of the Fas/Fas-ligand system has potential prognostic application in view of current knowledge, and consequently should be considered as an additional prognostic factor in breast cancer patients.
    Contemporary Oncology / Wspólczesna Onkologia 04/2013; 17(2):120-122. DOI:10.5114/wo.2013.34612 · 0.22 Impact Factor
Show more