DcR1 expression in endometrial carcinomas.
The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which mediates apoptosis by the extrinsic pathway. Up-regulation of decoy receptors, DcR1 and DcR2, may result in diminished binding of TRAIL to their functional receptors. DcR1 expression was assessed in normal endometrial tissue (NE) and endometrial carcinoma (EC) samples by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (PCR). IHC was performed in two tissue microarrays; one composed of 80 samples of NE and a second one constructed from paraffin-embedded blocks of 62 EC. For quantitative real-time RT-PCR analysis, RNA was obtained from 19 NE and 28 EC samples using Trizol. mRNA expression of DcR1 was assessed with Taqman-based assays in an Abi-Prism 700 SDS. Results were correlated with stage, histological type, and grade. By IHC, cytoplasmic expression of DcR1 was frequently seen in NE (79.6%) and varied according to the menstrual cycle. Positive DcR1 immunostaining was also detected in EC (98.1% of the cases) without any specific statistical association with histological type, grade, and stage. By quantitative real-time PCR, all NE had similar levels of DcR1expression (0.8-1.7 RQ), which were considered the basal levels of DcR1 expression in NE. Increased DcR1 expression (> or =5-fold higher than the basal levels) was detected in 13 of 28 EC (46.4%). High DcR1 expression levels were found in ECs of different stages: IA, four of 12 (33%); IB, two of four (50%); IC, four of six (66%); and IIA and IIB three of six (50%). Results suggest that DcR1 expression occurs in a subset of EC and may contribute to resistance to TRAIL-induced apoptosis.
Tarragona
Jordi
J
Department of Pathology and Molecular Genetics, Hospital Universitari Arnau de Vilanova, University of Lleida IRBLLEIDA, Av Alcalde Rovira Roure 80, 25198 Lleida, Spain. tarragona@gss.scs.e
Llecha
Nuria
N
Santacana
Maria
M
Lopez
Susana
S
Gatius
Sonia
S
Llobet
David
D
Dolcet
Xavier
X
Palomar-Asenjo
Victor
V
Gonzalez-Tallada
Francisco Javier
FJ
Matias-Guiu
Xavier
X
D017209:Apoptosis / Q000502:physiology; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D046228:Microarray Analysis; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000096:biosynthesis / Q000235:genetics
D058851:GPI-Linked Proteins; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C108661:TNFRSF10C protein, human; D053319:Tumor Necrosis Factor Decoy Receptors