The role of E-Cadherin expression in primary site of breast cancer.

PURPOSE: The tumour's ability to metastasize is the major cause for fatal outcomes in cancer diseases. In breast cancer, aberrant E-Cadherin expression has been linked to invasiveness and poor prognosis. METHOD: We assessed expression of E-Cadherin by immunohistochemistry in primary tumour tissue from 125 female breast cancer patients. Staining intensities were analysed using the immunoreactive score (IRS). We investigated E-Cadherin expression and its associations with clinicopathological parameters (age, tumour size, lymph node status, grade, hormone receptors, Her2 Status) as well as with recurrence and survival. RESULTS: Increased, rather than aberrant E-Cadherin expression was found and was associated with poor outcome (p = 0.046). Our data show an association between elevated E-Cadherin in primary tumour tissue and an unfavourable negative prognosis in patients. CONCLUSION: This association was somehow unexpected as loss of E-Cadherin has long been regarded as a prerequisite for development of invasiveness and metastases. Our findings support the notion that E-Cadherin promotes, rather than suppresses, development of metastasis and invasiveness.

Induction of apoptosis in breast cancer cells in vitro by Fas ligand reverse signaling.

PURPOSE: The Fas-antigen is a cell surface receptor that transduces apoptotic signals into cells. The purpose of this study was to evaluate FasL expression in breast cancer and to elucidate the role of its signaling in different breast cancer cell lines. METHODS: T47D and MCF7 cells were used and cultured in Dulbecco's modified Eagle's medium. FasL translocation to the membrane was achieved by culturing the cells in the presence of human interferon-γ (IFNγ). Translocation was detected by immunofluorescence. The ability of a Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by cell death detection ELISA. After incubation with IFNγ for 4 h and 18 h, apoptosis was assessed in response to treatment with Fas:Fc. RESULTS: Immunofluorescence revealed that the used cell lines were positive for FasL which was increased and changed to more membrane-bound FasL expression after IFNγ stimulation. After stimulation with 50 IU/ml IFNγ, Fas:Fc significantly increased MCF7 apoptosis (1.39 ± 0.06-fold, p = 0.0004) after 18 h. After stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4 h (1.49 ± 0.15-fold, p = 0.018) and 18 h (1.30 ± 0.06-fold, p = 0.013). In T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and addition of Fas:Fc (1.6 ± 0.08-fold, p = 0.03). CONCLUSION: Membrane-bound FasL expression could be induced by IFNγ in a breast cancer cell model. More importantly, in the presence of IFNγ the Fas:Fc fusion protein was able to transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing apoptosis. The current findings support further in vivo studies regarding FasL activation as a potential target for therapeutic intervention in breast cancer.