%0 Journal Article
%T Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells
%A Ahter D Sanlioglu
%A Ercument Dirice
%A Cigdem Aydin
%A Nuray Erin
%A Sadi Koksoy
%A Salih Sanlioglu
%J BMC Cancer
%D 2005
%I BioMed Central
%R 10.1186/1471-2407-5-54
%X TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells.MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKK¦ÂKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4 expression. Furthermore, a DcR2 siRNA approach lowered TRAIL-R4 expression on surface and this sensitized MCF7 cells to TRAIL.The expression of TRAIL-R4 decoy receptor appeared to be well correlated with TRAIL resistance encountered in breast cancer cells. Both adenovirus mediated IKK¦ÂKA expression and a DcR2 siRNA approach sensitized MCF7 breast cancer cells to TRAIL.Cancer still appears to be a challenging disease to treat. According to most recent estimates, more than 10 million new cancer cases were reported in the year 2000 killing around 6 million people [1]. In addition, 10 % of all cancers appear to be the breast cancer. Being the most frequently diagnosed cancer type in women, the breast cancer claims about 370,000 deaths each year around the world [2]. Surgery, radiotherapy and chemoth
%U http://www.biomedcentral.com/1471-2407/5/54