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Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-γ as a prognostic marker

Authors: Andreas Krieg, Sabrina Mersch, Nadine Wolf, Nikolas H Stoecklein, Pablo E Verde, Jan Schulte am Esch 2nd, Sebastian Heikaus, Helmut E Gabbert, Wolfram T Knoefel, Csaba Mahotka

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

TNF-related apoptosis inducing ligand (TRAIL) belongs to the TNF-superfamily that induces apoptotic cell death in a wide range of neoplastic cells in vivo as well as in vitro. We identified two alternative TRAIL-splice variants, i.e. TRAIL-β and TRAIL-γ that are characterized by the loss of their proapoptotic properties. Herein, we investigated the expression and the prognostic values of the TRAIL-splice variants in gastric carcinomas.

Methods

Real time PCR for amplification of the TRAIL-splice variants was performed in tumour tissue specimens and corresponding normal tissues of 41 consecutive patients with gastric carcinoma. Differences on mRNA-expression levels of the TRAIL-isoforms were compared to histo-pathological variables and correlated with survival data.

Results

All three TRAIL-splice variants could be detected in both non-malignant and malignant tissues, irrespective of their histological staging, grading or tumour types. However, TRAIL-β exhibited a higher expression in normal gastric tissue. The proapoptotic TRAIL-α expression was increased in gastric carcinomas when compared to TRAIL-β and TRAIL-γ. In addition, overexpression of TRAIL-γ was associated with a significant higher survival rate.

Conclusions

This is the first study that investigated the expression of TRAIL-splice variants in gastric carcinoma tissue samples. Thus, we provide first data that indicate a prognostic value for TRAIL-γ overexpression in this tumour entity.
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Literature
1.
go back to reference Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A: Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 1996, 271 (22): 12687-12690. 10.1074/jbc.271.22.12687.CrossRefPubMed Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A: Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem. 1996, 271 (22): 12687-12690. 10.1074/jbc.271.22.12687.CrossRefPubMed
2.
go back to reference Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995, 3 (6): 673-682. 10.1016/1074-7613(95)90057-8.CrossRefPubMed Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995, 3 (6): 673-682. 10.1016/1074-7613(95)90057-8.CrossRefPubMed
3.
go back to reference Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, et al: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999, 104 (2): 155-162. 10.1172/JCI6926.CrossRefPubMedPubMedCentral Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, et al: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 1999, 104 (2): 155-162. 10.1172/JCI6926.CrossRefPubMedPubMedCentral
4.
go back to reference Dejosez M, Ramp U, Mahotka C, Krieg A, Walczak H, Gabbert HE, Gerharz CD: Sensitivity to TRAIL/APO-2L-mediated apoptosis in human renal cell carcinomas and its enhancement by topotecan. Cell Death Differ. 2000, 7 (11): 1127-1136. 10.1038/sj.cdd.4400746.CrossRefPubMed Dejosez M, Ramp U, Mahotka C, Krieg A, Walczak H, Gabbert HE, Gerharz CD: Sensitivity to TRAIL/APO-2L-mediated apoptosis in human renal cell carcinomas and its enhancement by topotecan. Cell Death Differ. 2000, 7 (11): 1127-1136. 10.1038/sj.cdd.4400746.CrossRefPubMed
5.
go back to reference Gura T: How TRAIL kills cancer cells, but not normal cells. Science. 1997, 277 (5327): 768-10.1126/science.277.5327.768.CrossRefPubMed Gura T: How TRAIL kills cancer cells, but not normal cells. Science. 1997, 277 (5327): 768-10.1126/science.277.5327.768.CrossRefPubMed
6.
go back to reference Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, et al: Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 1997, 277 (5327): 818-821. 10.1126/science.277.5327.818.CrossRefPubMed Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, et al: Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science. 1997, 277 (5327): 818-821. 10.1126/science.277.5327.818.CrossRefPubMed
7.
go back to reference Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, et al: TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. Embo J. 1997, 16 (17): 5386-5397. 10.1093/emboj/16.17.5386.CrossRefPubMedPubMedCentral Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, et al: TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. Embo J. 1997, 16 (17): 5386-5397. 10.1093/emboj/16.17.5386.CrossRefPubMedPubMedCentral
8.
go back to reference Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, et al: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 1999, 5 (2): 157-163. 10.1038/5517.CrossRefPubMed Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, et al: Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med. 1999, 5 (2): 157-163. 10.1038/5517.CrossRefPubMed
9.
go back to reference Dimberg LY, Anderson CK, Camidge R, Behbakht K, Thorburn A, Ford HL: On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics. Oncogene. 2013, 32 (11): 1341-1350. 10.1038/onc.2012.164.CrossRefPubMed Dimberg LY, Anderson CK, Camidge R, Behbakht K, Thorburn A, Ford HL: On the TRAIL to successful cancer therapy? Predicting and counteracting resistance against TRAIL-based therapeutics. Oncogene. 2013, 32 (11): 1341-1350. 10.1038/onc.2012.164.CrossRefPubMed
10.
go back to reference Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG: The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity. 1997, 7 (6): 813-820. 10.1016/S1074-7613(00)80399-4.CrossRefPubMed Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG: The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity. 1997, 7 (6): 813-820. 10.1016/S1074-7613(00)80399-4.CrossRefPubMed
11.
go back to reference Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA: Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med. 1997, 186 (7): 1165-1170. 10.1084/jem.186.7.1165.CrossRefPubMedPubMedCentral Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA: Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med. 1997, 186 (7): 1165-1170. 10.1084/jem.186.7.1165.CrossRefPubMedPubMedCentral
12.
go back to reference Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, et al: Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998, 273 (23): 14363-14367. 10.1074/jbc.273.23.14363.CrossRefPubMed Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, et al: Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998, 273 (23): 14363-14367. 10.1074/jbc.273.23.14363.CrossRefPubMed
13.
go back to reference MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES: Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J Biol Chem. 1997, 272 (41): 25417-25420. 10.1074/jbc.272.41.25417.CrossRefPubMed MacFarlane M, Ahmad M, Srinivasula SM, Fernandes-Alnemri T, Cohen GM, Alnemri ES: Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J Biol Chem. 1997, 272 (41): 25417-25420. 10.1074/jbc.272.41.25417.CrossRefPubMed
14.
go back to reference Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, et al: A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol. 1997, 7 (12): 1003-1006. 10.1016/S0960-9822(06)00422-2.CrossRefPubMed Marsters SA, Sheridan JP, Pitti RM, Huang A, Skubatch M, Baldwin D, Yuan J, Gurney A, Goddard AD, Godowski P, et al: A novel receptor for Apo2L/TRAIL contains a truncated death domain. Curr Biol. 1997, 7 (12): 1003-1006. 10.1016/S0960-9822(06)00422-2.CrossRefPubMed
15.
go back to reference Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM: An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 1997, 277 (5327): 815-818. 10.1126/science.277.5327.815.CrossRefPubMed Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM: An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science. 1997, 277 (5327): 815-818. 10.1126/science.277.5327.815.CrossRefPubMed
16.
go back to reference Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM: The receptor for the cytotoxic ligand TRAIL. Science. 1997, 276 (5309): 111-113. 10.1126/science.276.5309.111.CrossRefPubMed Pan G, O'Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, Dixit VM: The receptor for the cytotoxic ligand TRAIL. Science. 1997, 276 (5309): 111-113. 10.1126/science.276.5309.111.CrossRefPubMed
17.
go back to reference Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000, 12 (6): 611-620. 10.1016/S1074-7613(00)80212-5.CrossRefPubMed Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity. 2000, 12 (6): 611-620. 10.1016/S1074-7613(00)80212-5.CrossRefPubMed
18.
go back to reference Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P, Blenis J, Tschopp J: TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol. 2000, 2 (4): 241-243. 10.1038/35008667.CrossRefPubMed Bodmer JL, Holler N, Reynard S, Vinciguerra P, Schneider P, Juo P, Blenis J, Tschopp J: TRAIL receptor-2 signals apoptosis through FADD and caspase-8. Nat Cell Biol. 2000, 2 (4): 241-243. 10.1038/35008667.CrossRefPubMed
19.
go back to reference Kuang AA, Diehl GE, Zhang J, Winoto A: FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. J Biol Chem. 2000, 275 (33): 25065-25068. 10.1074/jbc.C000284200.CrossRefPubMed Kuang AA, Diehl GE, Zhang J, Winoto A: FADD is required for DR4- and DR5-mediated apoptosis: lack of trail-induced apoptosis in FADD-deficient mouse embryonic fibroblasts. J Biol Chem. 2000, 275 (33): 25065-25068. 10.1074/jbc.C000284200.CrossRefPubMed
20.
go back to reference Miyazaki T, Reed JC: A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins. Nat Immunol. 2001, 2 (6): 493-500. 10.1038/88684.CrossRefPubMed Miyazaki T, Reed JC: A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins. Nat Immunol. 2001, 2 (6): 493-500. 10.1038/88684.CrossRefPubMed
21.
go back to reference Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH, Walczak H: FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity. 2000, 12 (6): 599-609. 10.1016/S1074-7613(00)80211-3.CrossRefPubMed Sprick MR, Weigand MA, Rieser E, Rauch CT, Juo P, Blenis J, Krammer PH, Walczak H: FADD/MORT1 and caspase-8 are recruited to TRAIL receptors 1 and 2 and are essential for apoptosis mediated by TRAIL receptor 2. Immunity. 2000, 12 (6): 599-609. 10.1016/S1074-7613(00)80211-3.CrossRefPubMed
22.
go back to reference Mongkolsapaya J, Cowper AE, Xu XN, Morris G, McMichael AJ, Bell JI, Screaton GR: Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL. J Immunol. 1998, 160 (1): 3-6.PubMed Mongkolsapaya J, Cowper AE, Xu XN, Morris G, McMichael AJ, Bell JI, Screaton GR: Lymphocyte inhibitor of TRAIL (TNF-related apoptosis-inducing ligand): a new receptor protecting lymphocytes from the death ligand TRAIL. J Immunol. 1998, 160 (1): 3-6.PubMed
23.
go back to reference Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L: Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity. 1997, 7 (6): 821-830. 10.1016/S1074-7613(00)80400-8.CrossRefPubMed Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L: Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway. Immunity. 1997, 7 (6): 821-830. 10.1016/S1074-7613(00)80400-8.CrossRefPubMed
24.
go back to reference Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J: TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity. 1997, 7 (6): 831-836. 10.1016/S1074-7613(00)80401-X.CrossRefPubMed Schneider P, Thome M, Burns K, Bodmer JL, Hofmann K, Kataoka T, Holler N, Tschopp J: TRAIL receptors 1 (DR4) and 2 (DR5) signal FADD-dependent apoptosis and activate NF-kappaB. Immunity. 1997, 7 (6): 831-836. 10.1016/S1074-7613(00)80401-X.CrossRefPubMed
25.
go back to reference Hu WH, Johnson H, Shu HB: Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways. J Biol Chem. 1999, 274 (43): 30603-30610. 10.1074/jbc.274.43.30603.CrossRefPubMed Hu WH, Johnson H, Shu HB: Tumor necrosis factor-related apoptosis-inducing ligand receptors signal NF-kappaB and JNK activation and apoptosis through distinct pathways. J Biol Chem. 1999, 274 (43): 30603-30610. 10.1074/jbc.274.43.30603.CrossRefPubMed
26.
go back to reference Secchiero P, Gonelli A, Carnevale E, Milani D, Pandolfi A, Zella D, Zauli G: TRAIL promotes the survival and proliferation of primary human vascular endothelial cells by activating the Akt and ERK pathways. Circulation. 2003, 107 (17): 2250-2256. 10.1161/01.CIR.0000062702.60708.C4.CrossRefPubMed Secchiero P, Gonelli A, Carnevale E, Milani D, Pandolfi A, Zella D, Zauli G: TRAIL promotes the survival and proliferation of primary human vascular endothelial cells by activating the Akt and ERK pathways. Circulation. 2003, 107 (17): 2250-2256. 10.1161/01.CIR.0000062702.60708.C4.CrossRefPubMed
27.
go back to reference Tran SE, Holmstrom TH, Ahonen M, Kahari VM, Eriksson JE: MAPK/ERK overrides the apoptotic signaling from Fas, TNF, and TRAIL receptors. J Biol Chem. 2001, 276 (19): 16484-16490. 10.1074/jbc.M010384200.CrossRefPubMed Tran SE, Holmstrom TH, Ahonen M, Kahari VM, Eriksson JE: MAPK/ERK overrides the apoptotic signaling from Fas, TNF, and TRAIL receptors. J Biol Chem. 2001, 276 (19): 16484-16490. 10.1074/jbc.M010384200.CrossRefPubMed
28.
go back to reference Ehrhardt H, Fulda S, Schmid I, Hiscott J, Debatin KM, Jeremias I: TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene. 2003, 22 (25): 3842-3852. 10.1038/sj.onc.1206520.CrossRefPubMed Ehrhardt H, Fulda S, Schmid I, Hiscott J, Debatin KM, Jeremias I: TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene. 2003, 22 (25): 3842-3852. 10.1038/sj.onc.1206520.CrossRefPubMed
29.
go back to reference Trauzold A, Siegmund D, Schniewind B, Sipos B, Egberts J, Zorenkov D, Emme D, Roder C, Kalthoff H, Wajant H: TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene. 2006, 25 (56): 7434-7439. 10.1038/sj.onc.1209719.CrossRefPubMed Trauzold A, Siegmund D, Schniewind B, Sipos B, Egberts J, Zorenkov D, Emme D, Roder C, Kalthoff H, Wajant H: TRAIL promotes metastasis of human pancreatic ductal adenocarcinoma. Oncogene. 2006, 25 (56): 7434-7439. 10.1038/sj.onc.1209719.CrossRefPubMed
30.
go back to reference Maduro JH, Noordhuis MG, ten Hoor KA, Pras E, Arts HJ, Eijsink JJ, Hollema H, Mom CH, de Jong S, de Vries EG, et al: The prognostic value of TRAIL and its death receptors in cervical cancer. Int J Radiat Oncol Biol Phys. 2009, 75 (1): 203-211. 10.1016/j.ijrobp.2009.03.071.CrossRefPubMed Maduro JH, Noordhuis MG, ten Hoor KA, Pras E, Arts HJ, Eijsink JJ, Hollema H, Mom CH, de Jong S, de Vries EG, et al: The prognostic value of TRAIL and its death receptors in cervical cancer. Int J Radiat Oncol Biol Phys. 2009, 75 (1): 203-211. 10.1016/j.ijrobp.2009.03.071.CrossRefPubMed
31.
go back to reference Spierings DC, de Vries EG, Timens W, Groen HJ, Boezen HM, de Jong S: Expression of TRAIL and TRAIL death receptors in stage III non-small cell lung cancer tumors. Clin Cancer Res. 2003, 9 (9): 3397-3405.PubMed Spierings DC, de Vries EG, Timens W, Groen HJ, Boezen HM, de Jong S: Expression of TRAIL and TRAIL death receptors in stage III non-small cell lung cancer tumors. Clin Cancer Res. 2003, 9 (9): 3397-3405.PubMed
32.
go back to reference McLornan DP, Barrett HL, Cummins R, McDermott U, McDowell C, Conlon SJ, Coyle VM, Van Schaeybroeck S, Wilson R, Kay EW, et al: Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer. Clin Cancer Res. 2010, 16 (13): 3442-3451. 10.1158/1078-0432.CCR-10-0052.CrossRefPubMedPubMedCentral McLornan DP, Barrett HL, Cummins R, McDermott U, McDowell C, Conlon SJ, Coyle VM, Van Schaeybroeck S, Wilson R, Kay EW, et al: Prognostic significance of TRAIL signaling molecules in stage II and III colorectal cancer. Clin Cancer Res. 2010, 16 (13): 3442-3451. 10.1158/1078-0432.CCR-10-0052.CrossRefPubMedPubMedCentral
33.
go back to reference Jiang ZH, Wu JY: Alternative splicing and programmed cell death. Proc Soc Exp Biol Med. 1999, 220 (2): 64-72. 10.3181/00379727-220-44346.CrossRefPubMed Jiang ZH, Wu JY: Alternative splicing and programmed cell death. Proc Soc Exp Biol Med. 1999, 220 (2): 64-72. 10.3181/00379727-220-44346.CrossRefPubMed
34.
go back to reference Schwerk C, Schulze-Osthoff K: Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell. 2005, 19 (1): 1-13. 10.1016/j.molcel.2005.05.026.CrossRefPubMed Schwerk C, Schulze-Osthoff K: Regulation of apoptosis by alternative pre-mRNA splicing. Mol Cell. 2005, 19 (1): 1-13. 10.1016/j.molcel.2005.05.026.CrossRefPubMed
35.
go back to reference Krieg A, Krieg T, Wenzel M, Schmitt M, Ramp U, Fang B, Gabbert HE, Gerharz CD, Mahotka C: TRAIL-beta and TRAIL-gamma: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential. Br J Cancer. 2003, 88 (6): 918-927. 10.1038/sj.bjc.6600772.CrossRefPubMedPubMedCentral Krieg A, Krieg T, Wenzel M, Schmitt M, Ramp U, Fang B, Gabbert HE, Gerharz CD, Mahotka C: TRAIL-beta and TRAIL-gamma: two novel splice variants of the human TNF-related apoptosis-inducing ligand (TRAIL) without apoptotic potential. Br J Cancer. 2003, 88 (6): 918-927. 10.1038/sj.bjc.6600772.CrossRefPubMedPubMedCentral
36.
go back to reference Krieg A, Schulte am Esch J, Ramp U, Hosch SB, Knoefel WT, Gabbert HE, Mahotka C: TRAIL-R4-beta: a new splice variant of TRAIL-receptor 4 lacking the cysteine rich domain 1. Biochem Biophys Res Commun. 2006, 349 (1): 115-121. 10.1016/j.bbrc.2006.08.031.CrossRefPubMed Krieg A, Schulte am Esch J, Ramp U, Hosch SB, Knoefel WT, Gabbert HE, Mahotka C: TRAIL-R4-beta: a new splice variant of TRAIL-receptor 4 lacking the cysteine rich domain 1. Biochem Biophys Res Commun. 2006, 349 (1): 115-121. 10.1016/j.bbrc.2006.08.031.CrossRefPubMed
37.
go back to reference Koyama S, Koike N, Adachi S: Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor. J Cancer Res Clin Oncol. 2002, 128 (2): 73-79. 10.1007/s004320100292.CrossRefPubMed Koyama S, Koike N, Adachi S: Expression of TNF-related apoptosis-inducing ligand (TRAIL) and its receptors in gastric carcinoma and tumor-infiltrating lymphocytes: a possible mechanism of immune evasion of the tumor. J Cancer Res Clin Oncol. 2002, 128 (2): 73-79. 10.1007/s004320100292.CrossRefPubMed
38.
go back to reference Watanabe H, Jass JR, Sobin LH: WHO International Classification of Tumours. Histological typing of oesophageal and gastric tumours. 1998, New York: Springer-Verlag, 2 Watanabe H, Jass JR, Sobin LH: WHO International Classification of Tumours. Histological typing of oesophageal and gastric tumours. 1998, New York: Springer-Verlag, 2
39.
go back to reference Sobin LH, Wittekind C: TNM classification of malignant tumors. 1997, New York: Wiley-Liss, 5 Sobin LH, Wittekind C: TNM classification of malignant tumors. 1997, New York: Wiley-Liss, 5
40.
go back to reference Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987, 162 (1): 156-159.CrossRefPubMed Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987, 162 (1): 156-159.CrossRefPubMed
41.
go back to reference Bennett MW, O'Connell J, O'Sullivan GC, Brady C, Roche D, Collins JK, Shanahan F: The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol. 1998, 160 (11): 5669-5675.PubMed Bennett MW, O'Connell J, O'Sullivan GC, Brady C, Roche D, Collins JK, Shanahan F: The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J Immunol. 1998, 160 (11): 5669-5675.PubMed
42.
go back to reference Ryan AE, Lane S, Shanahan F, O'Connell J, Houston AM: Fas ligand expression in human and mouse cancer cell lines; a caveat on over-reliance on mRNA data. J Carcinog. 2006, 5: 5-10.1186/1477-3163-5-5.CrossRefPubMedPubMedCentral Ryan AE, Lane S, Shanahan F, O'Connell J, Houston AM: Fas ligand expression in human and mouse cancer cell lines; a caveat on over-reliance on mRNA data. J Carcinog. 2006, 5: 5-10.1186/1477-3163-5-5.CrossRefPubMedPubMedCentral
43.
go back to reference Ryan KR, McCue D, Anderton SM: Fas-mediated death and sensory adaptation limit the pathogenic potential of autoreactive T cells after strong antigenic stimulation. J Leukoc Biol. 2005, 78 (1): 43-50. 10.1189/jlb.0205059.CrossRefPubMed Ryan KR, McCue D, Anderton SM: Fas-mediated death and sensory adaptation limit the pathogenic potential of autoreactive T cells after strong antigenic stimulation. J Leukoc Biol. 2005, 78 (1): 43-50. 10.1189/jlb.0205059.CrossRefPubMed
Metadata
Title
Expression of TRAIL-splice variants in gastric carcinomas: identification of TRAIL-γ as a prognostic marker
Authors
Andreas Krieg
Sabrina Mersch
Nadine Wolf
Nikolas H Stoecklein
Pablo E Verde
Jan Schulte am Esch 2nd
Sebastian Heikaus
Helmut E Gabbert
Wolfram T Knoefel
Csaba Mahotka
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-384

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