8742

TNFSF12

tumor necrosis factor (ligand) superfamily, member 12;TNFSF12;tumor necrosis factor (ligand) superfamily, member 12

APO3 ligand|APO3/DR3 ligand|TNF-related WEAK inducer of apoptosis|tumor necrosis factor ligand superfamily member 12

17p13

protein-coding

BACKGROUND & OBJECTIVE: The expression of TNF-like weak inducer of apoptosis (TWEAK) in breast cancer remains disputable. This study was to investigate the expression of TWEAK in breast cancer tissues and breast cancer cell lines with different invasive abilities, and the relationship of TWEAK with microvessel density (MVD). METHODS: Immunohistochemical S-P method was adopted to detect the expression of TWEAK in 70 specimens of breast cancer and 30 specimens of adjacent normal breast tissues. The protein expression of TWEAK was determined by Western blot in a poorly invasive breast cancer cell line MCF-7 and a highly invasive breast cell line MDA-MB-231. Secretion of TWEAK was measured by ELISA assay in MCF-7 and MDA-MB-231 cells. RESULTS: The expression of TWEAK was higher in breast cancer (60%) than in adjacent normal breast tissues( 6.67%) (P<0.05), and is higher in infiltrating ductal carcinoma of the breast (76.67 %) than in breast ductal carcinoma in situ (42.85%) (P=0.003). MVD was higher in infiltrating ductal carcinoma of the breast than in breast ductal carcinoma in situ (P<0.05). The expression of TWEAK was significantly correlated with MVD in infiltrating ductal carcinoma of the breast(r=0.611), but not with breast ductal carcinoma in situ (r=0.015). The expression of TWEAK and secretion of soluble TWEAK were higher in MDA-MB-231 cells than in MCF-7 cells (t=4.259, P=0.007; t=3.6504, P=0.006 ). CONCLUSION: TWEAK expression is related to the metastatic ability of breast cancer.

The poor prognosis of human ovarian cancer is partly due to its metastasis and recurrence. It has been demonstrated that tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK)-fibroblast growth factor inducible-14 (Fn14) signaling system may be a potential regulator of human tumorigenesis. The objective of this study was to understand the effect of TWEAK on ovarian cancer metastasis. We recently showed that activation of Fn14 signaling by TWEAK promoted cell migration and invasion in human HO-8910PM cells. Treating HO-8910PM cells with TWEAK resulted in the activation of nuclear factor-kappa B (NF-kappaB) and subsequently the translocation of NF-kappaB from cytoplasm to nucleus. In addition, TWEAK promoted vascular endothelial growth factor (VEGF) protein expression, and this effect was dependent upon NF-kappaB transcriptional activity. Blocking the NF-kappaB pathway with PDTC suppressed TWEAK-induced up-regulation of VEGF protein expression and cell metastasis. Our results suggest that TWEAK-Fn14 functions, in part, through the NF-kappaB signaling pathway to up-regulate VEGF expression to foster ovarian cancer cell metastasis. Targeted therapy against TWEAK-Fn14 signaling system as an adjuvant to surgery may improve clinical management of invasive ovarian cancer cells and advance the outcome of this devastating cancer.