Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Activation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene expression following DNA demethylation in placental choriocarcinoma and transformed cell lines

Pan-Hong Wu A , Xue-Mei Chen A , Xue-Qing Liu A , Jun-Lin He A , Qian Feng A , Xi Lan A , Xue Zhang A , Yan-Qing Geng A , Ying-Xiong Wang A and Yu-Bin Ding A B
+ Author Affiliations
- Author Affiliations

A Laboratory of Reproductive Biology, School of Public Health and Management, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, 400016 Chongqing, PR China.

B Corresponding author. Email: dingyb@gmail.com

Reproduction, Fertility and Development 28(11) 1844-1853 https://doi.org/10.1071/RD14408
Submitted: 26 October 2014  Accepted: 29 April 2015   Published: 27 May 2015

Abstract

We characterised DNA methylation and gene expression of four tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4, DR5, DcR1 and DcR2 in three choriocarcinoma (JAR, JEG-3, BeWo) and two transformed (HTR-8/SVneo and HPT-8) cell lines. DR4 mRNA was detected in JAR, JEG-3, BeWo and HTR-8/SVneo cells, whereas DR5 was present in all detected cells. DcR1 transcripts were expressed only in JAR, JEG-3 and BeWo cells, whereas DcR2 transcripts were detected only in HTR-8/SVneo and HPT-8 cells. Hypermethylated DR4 promoter was observed in JAR, JEG-3, BeWo and HTR-8/SVneo cells, hypermethylated DcR1 promoter in HTR-8/SVneo and HPT-8 cells and hypermethylated DcR2 promoter in JAR, JEG-3 and BeWo cells. Restoration of DR4, DcR1 and DcR2 expression with decreased DNA methylation of these genes was induced by the DNA demethylation agent 5-aza-2′-deoxycytidine (5-aza-CdR) in trophoblast cells, whereas DR5 expression did not exhibit any change. Significant negative correlation between the expression and DNA methylation of these genes was also observed. In all tested cell lines, only HPT-8 demonstrated sensitivity to TRAIL-induced apoptosis. Combined treatment with 5-aza-CdR and TRAIL resulted in apoptosis in JAR, JEG-3, BeWo and HTR-8/SVneo cells but not in HPT-8 cells. The results indicate that DNA methylation is associated with TRAIL receptor expression and might be involved in trophoblast apoptosis.

Additional keywords: apoptosis, DNA methylation, trophoblast.


References

Agostinis, C., Bulla, R., Tisato, V., De Seta, F., Alberico, S., Secchiero, P., and Zauli, G. (2012). Soluble TRAIL is elevated in recurrent miscarriage and inhibits the in vitro adhesion and migration of HTR8 trophoblastic cells. Hum. Reprod. 27, 2941–2947.
Soluble TRAIL is elevated in recurrent miscarriage and inhibits the in vitro adhesion and migration of HTR8 trophoblastic cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhtlymsbnF&md5=921de938f42e5aef7abb59ea571eb0bdCAS | 22914768PubMed |

Bae, S. I., Cheriyath, V., Jacobs, B. S., Reu, F. J., and Borden, E. C. (2008). Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL. Oncogene 27, 490–498.
Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnt1Cjtw%3D%3D&md5=518e8c4bcf70a7debaf33a9c770a8a4eCAS | 17653094PubMed |

Bai, X., Williams, J. L., Greenwood, S. L., Baker, P. N., Aplin, J. D., and Crocker, I. P. (2009). A placental protective role for trophoblast-derived TNF-related apoptosis-inducing ligand (TRAIL). Placenta 30, 855–860.
A placental protective role for trophoblast-derived TNF-related apoptosis-inducing ligand (TRAIL).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtFKgu7bK&md5=d9beaded7c4ae781d1febd3a838f7ec6CAS | 19674787PubMed |

Bamberger, A. M., Schulte, H. M., Thuneke, I., Erdmann, I., Bamberger, C. M., and Asa, S. L. (1997). Expression of the apoptosis-inducing Fas ligand (FasL) in human first and third trimester placenta and choriocarcinoma cells. J. Clin. Endocrinol. Metab. 82, 3173–3175.
Expression of the apoptosis-inducing Fas ligand (FasL) in human first and third trimester placenta and choriocarcinoma cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlvFemurs%3D&md5=4ecd8927c5c2f8e71c700092baad8290CAS | 9284765PubMed |

Baylin, S. B., and Herman, J. G. (2000). DNA hypermethylation in tumourigenesis: epigenetics joins genetics. Trends Genet. 16, 168–174.
DNA hypermethylation in tumourigenesis: epigenetics joins genetics.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXit1Sqsbg%3D&md5=31e2d3ecd3d3531453d889870afe19a6CAS | 10729832PubMed |

Brown, R., and Plumb, J. A. (2004). Demethylation of DNA by decitabine in cancer chemotherapy. Expert Rev. Anticancer Ther. 4, 501–510.
Demethylation of DNA by decitabine in cancer chemotherapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlvVOlurk%3D&md5=9b5def8e6b6f4d1404567374b3a967d3CAS | 15270655PubMed |

Chen, L., Liu, X., Zhu, Y., Cao, Y., Sun, L., and Jin, B. (2004). Localisation and variation of TRAIL and its receptors in human placenta during gestation. Life Sci. 74, 1479–1486.
Localisation and variation of TRAIL and its receptors in human placenta during gestation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXjsFWmsg%3D%3D&md5=4d0720de02bffa9f64b2649e44f5ac94CAS | 14729397PubMed |

Eggert, A., Grotzer, M. A., Zuzak, T. J., Wiewrodt, B. R., Ho, R., Ikegaki, N., and Brodeur, G. M. (2001). Resistance to tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression. Cancer Res. 61, 1314–1319.
| 1:CAS:528:DC%2BD3MXhvVelsbk%3D&md5=f2ee1393dea7f60f5bde5f7fc28ba7dfCAS | 11245427PubMed |

Elias, A., Siegelin, M. D., Steinmuller, A., von Deimling, A., Lass, U., Korn, B., and Mueller, W. (2009). Epigenetic silencing of death receptor 4 mediates tumour necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin. Cancer Res. 15, 5457–5465.
Epigenetic silencing of death receptor 4 mediates tumour necrosis factor-related apoptosis-inducing ligand resistance in gliomas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVOntrnN&md5=45724ef9e014549eeeb5f10a0b5c371fCAS | 19706813PubMed |

Fandy, T. E., Shankar, S., Ross, D. D., Sausville, E., and Srivastava, R. K. (2005). Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma. Neoplasia 7, 646–657.
Interactive effects of HDAC inhibitors and TRAIL on apoptosis are associated with changes in mitochondrial functions and expressions of cell cycle regulatory genes in multiple myeloma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXps1CntL4%3D&md5=cf9923425ac1a65c2da2331469fceb9bCAS | 16026644PubMed |

Flanagan, J. M., Cocciardi, S., Waddell, N., Johnstone, C. N., Marsh, A., Henderson, S., Simpson, P., da Silva, L., kConFab Investigators, Khanna, K., Lakhani, S., Boshoff, C., and Chenevix-Trench, G. (2010). DNA methylome of familial breast cancer identifies distinct profiles defined by mutation status. Am. J. Hum. Genet. 86, 420–433.
DNA methylome of familial breast cancer identifies distinct profiles defined by mutation status.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlt1Kntb4%3D&md5=bc0db2318bcbf0c50a0ed2634a3496e3CAS | 20206335PubMed |

Graham, C. H., Hawley, T. S., Hawley, R. G., MacDougall, J. R., Kerbel, R. S., Khoo, N., and Lala, P. K. (1993). Establishment and characterisation of first-trimester human trophoblast cells with extended lifespan. Exp. Cell Res. 206, 204–211.
Establishment and characterisation of first-trimester human trophoblast cells with extended lifespan.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXks1OisL0%3D&md5=3f875f981d94bbcf9d51c92d8df13433CAS | 7684692PubMed |

Held, J., and Schulze-Osthoff, K. (2001). Potential and caveats of TRAIL in cancer therapy. Drug Resist. Updat. 4, 243–252.
Potential and caveats of TRAIL in cancer therapy.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xkt1aktrs%3D&md5=7df94072fe58a9c43518e1438ade2428CAS | 11991679PubMed |

Higuchi, H., Grambihler, A., Canbay, A., Bronk, S. F., and Gores, G. J. (2004). Bile acids up-regulate death receptor 5/TRAIL-receptor 2 expression via a c-Jun N-terminal kinase-dependent pathway involving Sp1. J. Biol. Chem. 279, 51–60.
Bile acids up-regulate death receptor 5/TRAIL-receptor 2 expression via a c-Jun N-terminal kinase-dependent pathway involving Sp1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtVSqt7rP&md5=7bc379b434ea05c3e8fc54d8986a0bf2CAS | 14561739PubMed |

Hopkins-Donaldson, S., Ziegler, A., Kurtz, S., Bigosch, C., Kandioler, D., Ludwig, C., Zangemeister-Wittke, U., and Stahel, R. (2003). Silencing of death receptor and caspase-8 expression in small-cell lung carcinoma cell lines and tumours by DNA methylation. Cell Death Differ. 10, 356–364.
Silencing of death receptor and caspase-8 expression in small-cell lung carcinoma cell lines and tumours by DNA methylation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXivFGhtL4%3D&md5=f505739794185cea874e2c30c0a5bf57CAS | 12700635PubMed |

Horak, P., Pils, D., Haller, G., Pribill, I., Roessler, M., Tomek, S., Horvat, R., Zeillinger, R., Zielinski, C., and Krainer, M. (2005). Contribution of epigenetic silencing of tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol. Cancer Res. 3, 335–343.
Contribution of epigenetic silencing of tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXlsVWmur8%3D&md5=170a64ac126f457f6105810f45d7cc73CAS | 15972852PubMed |

Jerzak, M., and Bischof, P. (2002). Apoptosis in the first-trimester human placenta: the role in maintaining immune privilege at the maternal–fetal interface and in the trophoblast remodelling. Eur. J. Obstet. Gynecol. Reprod. Biol. 100, 138–142.
Apoptosis in the first-trimester human placenta: the role in maintaining immune privilege at the maternal–fetal interface and in the trophoblast remodelling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXpt1ams78%3D&md5=87de6456a9608bdc76d02c2e0bb7283fCAS | 11750952PubMed |

Karolchik, D., Baertsch, R., Diekhans, M., Furey, T. S., Hinrichs, A., Lu, Y. T., Roskin, K. M., Schwartz, M., Sugnet, C. W., Thomas, D. J., Weber, R. J., Haussler, D., and Kent, W. J. (2003). The UCSC Genome Browser Database. Nucleic Acids Res. 31, 51–54.
The UCSC Genome Browser Database.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhvFSgu7g%3D&md5=2058ce57c5b1f636b1220b4af7993c83CAS | 12519945PubMed |

Kurita, S., Higuchi, H., Saito, Y., Nakamoto, N., Takaishi, H., Tada, S., Saito, H., Gores, G. J., and Hibi, T. (2010). DNMT1 and DNMT3b silencing sensitises human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8. Cancer Sci. 101, 1431–1439.
DNMT1 and DNMT3b silencing sensitises human hepatoma cells to TRAIL-mediated apoptosis via up-regulation of TRAIL-R2/DR5 and caspase-8.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXns1Sks7c%3D&md5=6606ed475f1398ed56592970d0547470CAS | 20398055PubMed |

Lee, K. H., Lim, S. W., Kim, H. G., Kim, D. Y., Ryu, S. Y., Joo, J. K., Kim, J. C., and Lee, J. H. (2009). Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma. Langenbecks Arch. Surg. 394, 661–670.
Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma.Crossref | GoogleScholarGoogle Scholar | 19350268PubMed |

Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25, 402–408.
Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhtFelt7s%3D&md5=6db539426b70529f14f65734e4c1d0f6CAS | 11846609PubMed |

Lonergan, M., Aponso, D., Marvin, K. W., Helliwell, R. J., Sato, T. A., Mitchell, M. D., Chaiwaropongsa, T., Romero, R., and Keelan, J. A. (2003). Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labour at term and preterm. J. Clin. Endocrinol. Metab. 88, 3835–3844.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labour at term and preterm.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXmsFOktbo%3D&md5=8aa7b9d3ec641586fbf096c4961774a1CAS | 12915677PubMed |

MacFarlane, M., Ahmad, M., Srinivasula, S. M., Fernandes-Alnemri, T., Cohen, G. M., and Alnemri, E. S. (1997). Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL. J. Biol. Chem. 272, 25417–25420.
Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXms1Cqsr4%3D&md5=66b661b5ba0367bfc0453660903c6d51CAS | 9325248PubMed |

Margetts, C. D., Astuti, D., Gentle, D. C., Cooper, W. N., Cascon, A., Catchpoole, D., Robledo, M., Neumann, H. P., Latif, F., and Maher, E. R. (2005). Epigenetic analysis of HIC1, CASP8, FLIP, TSP1, DCR1, DCR2, DR4, DR5, KvDMR1, H19 and preferential 11p15.5 maternal-allele loss in von Hippel–Lindau and sporadic phaeochromocytomas. Endocr. Relat. Cancer 12, 161–172.
Epigenetic analysis of HIC1, CASP8, FLIP, TSP1, DCR1, DCR2, DR4, DR5, KvDMR1, H19 and preferential 11p15.5 maternal-allele loss in von Hippel–Lindau and sporadic phaeochromocytomas.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjsV2lsbo%3D&md5=aa6fcfd1fb36f41148b7452cdc2b2117CAS | 15788647PubMed |

Marsters, S. A., Pitti, R. M., Donahue, C. J., Ruppert, S., Bauer, K. D., and Ashkenazi, A. (1996). Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA. Curr. Biol. 6, 750–752.
Activation of apoptosis by Apo-2 ligand is independent of FADD but blocked by CrmA.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjvVGms70%3D&md5=aed515a594d372bab263394b89864106CAS | 8793301PubMed |

Meng, R. D., and El-Deiry, W. S. (2001). p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma. Exp. Cell Res. 262, 154–169.
p53-independent upregulation of KILLER/DR5 TRAIL receptor expression by glucocorticoids and interferon-gamma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnsVSk&md5=385879f61b19480d655eb518c0be214fCAS | 11139340PubMed |

Pan, G., O’Rourke, K., Chinnaiyan, A. M., Gentz, R., Ebner, R., Ni, J., and Dixit, V. M. (1997). The receptor for the cytotoxic ligand TRAIL. Science 276, 111–113.
The receptor for the cytotoxic ligand TRAIL.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXitl2jsL4%3D&md5=52f8d55a57a3b12ad7f274a56a1c3216CAS | 9082980PubMed |

Pan, G., Ni, J., Yu, G., Wei, Y. F., and Dixit, V. M. (1998). TRUNDD, a new member of the TRAIL receptor family that antagonises TRAIL signalling. FEBS Lett. 424, 41–45.
TRUNDD, a new member of the TRAIL receptor family that antagonises TRAIL signalling.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXhsFeju78%3D&md5=ab0811ae6101b89f30c2758d0082c35cCAS | 9537512PubMed |

Phillips, T. A., Ni, J., Pan, G., Ruben, S. M., Wei, Y. F., Pace, J. L., and Hunt, J. S. (1999). TRAIL (Apo-2L) and TRAIL receptors in human placentas: implications for immune privilege. J. Immunol. 162, 6053–6059.
| 1:CAS:528:DyaK1MXjt12lu74%3D&md5=4c91f95e47e4ae4554604a425b9a19d0CAS | 10229846PubMed |

Phillips, T. A., Ni, J., and Hunt, J. S. (2001). Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines. Placenta 22, 663–672.
Death-inducing tumour necrosis factor (TNF) superfamily ligands and receptors are transcribed in human placentae, cytotrophoblasts, placental macrophages and placental cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXotFaqu78%3D&md5=2a748485f9753b877c86214cc2814171CAS | 11597186PubMed |

Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A., and Ashkenazi, A. (1996). Induction of apoptosis by Apo-2 ligand, a new member of the tumour necrosis factor cytokine family. J. Biol. Chem. 271, 12687–12690.
Induction of apoptosis by Apo-2 ligand, a new member of the tumour necrosis factor cytokine family.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjtlGjtrc%3D&md5=9597bf3beb628df216f0a8d34da40b72CAS | 8663110PubMed |

Reu, F. J., Leaman, D. W., Maitra, R. R., Bae, S. I., Cherkassky, L., Fox, M. W., Rempinski, D. R., Beaulieu, N., MacLeod, A. R., and Borden, E. C. (2006). Expression of RASSF1A, an epigenetically silenced tumour suppressor, overcomes resistance to apoptosis induction by interferons. Cancer Res. 66, 2785–2793.
Expression of RASSF1A, an epigenetically silenced tumour suppressor, overcomes resistance to apoptosis induction by interferons.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhvV2gtrs%3D&md5=cf991bd98b86a26e298809b139cb3ab0CAS | 16510600PubMed |

Rubio-Moscardo, F., Blesa, D., Mestre, C., Siebert, R., Balasas, T., Benito, A., Rosenwald, A., Climent, J., Martinez, J. I., Schilhabel, M., Karran, E. L., Gesk, S., Esteller, M., deLeeuw, R., Staudt, L. M., Fernandez-Luna, J. L., Pinkel, D., Dyer, M. J., and Martinez-Climent, J. A. (2005). Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumour-suppressor genes. Blood 106, 3214–3222.
Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumour-suppressor genes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXht1WntrrO&md5=bf8a47609351eee58107d2b690aaa428CAS | 16051735PubMed |

Shankar, S., and Srivastava, R. K. (2004). Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist. Updat. 7, 139–156.
Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXkt1Wqu74%3D&md5=1f65323ba79649b6884de78c5ed9a391CAS | 15158769PubMed |

Sheridan, J. P., Marsters, S. A., Pitti, R. M., Gurney, A., Skubatch, M., Baldwin, D., Ramakrishnan, L., Gray, C. L., Baker, K., Wood, W. I., Goddard, A. D., Godowski, P., and Ashkenazi, A. (1997). Control of TRAIL-induced apoptosis by a family of signalling and decoy receptors. Science 277, 818–821.
Control of TRAIL-induced apoptosis by a family of signalling and decoy receptors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXlt1eks78%3D&md5=2ec2491984ca29b8cc101d23a4b1622dCAS | 9242611PubMed |

Shivapurkar, N., Toyooka, S., Toyooka, K. O., Reddy, J., Miyajima, K., Suzuki, M., Shigematsu, H., Takahashi, T., Parikh, G., Pass, H. I., Chaudhary, P. M., and Gazdar, A. F. (2004). Aberrant methylation of trail decoy receptor genes is frequent in multiple tumour types. Int. J. Cancer 109, 786–792.
Aberrant methylation of trail decoy receptor genes is frequent in multiple tumour types.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXivFCksr0%3D&md5=f6964f36b2d76b1b1dafc8a8a102b238CAS | 14999791PubMed |

Takimoto, R., and El-Deiry, W. S. (2000). Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site. Oncogene 19, 1735–1743.
Wild-type p53 transactivates the KILLER/DR5 gene through an intronic sequence-specific DNA-binding site.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjvFelt74%3D&md5=f1ff56860bd1ef152f445e07c53d457dCAS | 10777207PubMed |

Vähäkangas, K., and Myllynen, P. (2006). Experimental methods to study human transplacental exposure to genotoxic agents. Mutat. Res. 608, 129–135.
Experimental methods to study human transplacental exposure to genotoxic agents.Crossref | GoogleScholarGoogle Scholar | 16857420PubMed |

van Noesel, M. M., van Bezouw, S., Salomons, G. S., Voute, P. A., Pieters, R., Baylin, S. B., Herman, J. G., and Versteeg, R. (2002). Tumour-specific down-regulation of the tumour necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. Cancer Res. 62, 2157–2161.
| 1:CAS:528:DC%2BD38XivVylu7c%3D&md5=82ccf98ccd46b7bfbaa7cffba51fe74aCAS | 11929838PubMed |

Venza, M., Visalli, M., Catalano, T., Fortunato, C., Oteri, R., Teti, D., and Venza, I. (2013). Impact of DNA methyltransferases on the epigenetic regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in malignant melanoma. Biochem. Biophys. Res. Commun. 441, 743–750.
Impact of DNA methyltransferases on the epigenetic regulation of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor expression in malignant melanoma.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvVShu7fL&md5=67f328db0d03067d9d097903b501fd66CAS | 24211571PubMed |

Walczak, H., and Haas, T. L. (2008). Biochemical analysis of the native TRAIL death-inducing signalling complex. Methods Mol. Biol. 414, 221–239.
| 1:CAS:528:DC%2BD2sXhtlerurbM&md5=f7f75efbf644abde6d8b397d0697639fCAS | 18175822PubMed |

Walczak, H., Degli-Esposti, M. A., Johnson, R. S., Smolak, P. J., Waugh, J. Y., Boiani, N., Timour, M. S., Gerhart, M. J., Schooley, K. A., Smith, C. A., Goodwin, R. G., and Rauch, C. T. (1997). TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J. 16, 5386–5397.
TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXmsVGlsLo%3D&md5=a2ce6115c4262f24c4b33102823cc8eaCAS | 9311998PubMed |

Weng, Y. I., Huang, T. H., and Yan, P. S. (2009). Methylated DNA immunoprecipitation and microarray-based analysis: detection of DNA methylation in breast-cancer cell lines. Methods Mol. Biol. 590, 165–176.
Methylated DNA immunoprecipitation and microarray-based analysis: detection of DNA methylation in breast-cancer cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXos1CqtL8%3D&md5=4f700acfe36288ad21b70eb8daf0aa3eCAS | 19763503PubMed |

Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C., Smith, C. A., and Goodwin, R. G. (1995). Identification and characterisation of a new member of the TNF family that induces apoptosis. Immunity 3, 673–682.
Identification and characterisation of a new member of the TNF family that induces apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhtF2iug%3D%3D&md5=701c2291251ba90fa09f0177c4d263e9CAS | 8777713PubMed |

Yamanaka, T., Shiraki, K., Sugimoto, K., Ito, T., Fujikawa, K., Ito, M., Takase, K., Moriyama, M., Nakano, T., and Suzuki, A. (2000). Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines. Hepatology 32, 482–490.
Chemotherapeutic agents augment TRAIL-induced apoptosis in human hepatocellular carcinoma cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmsF2mtbk%3D&md5=411fc96e93cf8df4956781e446ffcd98CAS | 10960439PubMed |

Yang, Q., Kiernan, C. M., Tian, Y., Salwen, H. R., Chlenski, A., Brumback, B. A., London, W. B., and Cohn, S. L. (2007). Methylation of CASP8, DCR2 and HIN-1 in neuroblastoma is associated with poor outcome. Clin. Cancer Res. 13, 3191–3197.
Methylation of CASP8, DCR2 and HIN-1 in neuroblastoma is associated with poor outcome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXmtVajur8%3D&md5=549c93492289e9842fe06185702ef770CAS | 17545522PubMed |

Zhang, L., Zhang, W., Shao, C., Zhang, J., Men, K., Shao, Z., Yan, Y., and Xu, D. (2011). Establishment and characterisation of a spontaneously immortalised trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone. Hum. Reprod. 26, 2146–2156.
Establishment and characterisation of a spontaneously immortalised trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXptFCnsb0%3D&md5=bea5073e3c02b4b01819b8a8884d10b7CAS | 21596708PubMed |