Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 5/2014

01.05.2014 | Gynecologic Oncology

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors

verfasst von: Letícia da Conceição Braga, Luciana Maria Silva, Josiane Barbosa Piedade, Paulo Traiman, Agnaldo Lopes da Silva Filho

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 5/2014

Einloggen, um Zugang zu erhalten

Abstract

Objective

This study assesses TRAIL-R2 (TNF-related apoptosis-inducing ligand receptor 2) and BCL2 (B cell CLL/lymphoma 2) expression as well as CpG island methylation within the TRAIL-R2 promoter in ovarian serous tumors and primary and metastatic serous EOC (epithelial ovarian cancer).

Methods

RNA and DNA were obtained from women with normal ovarian tissues (n = 18), ovarian serous cystadenoma tumors (n = 11) and serous EOC (n = 16) using Trizol®. Quantitative PCR was performed to quantify the relative levels of TRAIL-R2 and BCL2. The methylation frequency of the TRAIL-R3 promoter was assessed using a methylation-specific PCR assay after DNA bisulfite conversion. Differences between the groups were evaluated using the χ 2, Mann–Whitney U or Kruskal–Wallis tests, as indicated.

Results

We identified TRAIL-R2 and BCL2 mRNA expressed in all ovarian tumor groups, and there were significant differences between the groups. Both genes had low expression levels in ovarian serous cystadenoma and primary EOC tumors when compared with metastatic EOC. Methylation of the TRAIL-R2 promoter was frequently observed in all groups; however, there were no statistically significant associations.

Conclusions

Primary EOC is associated with lower TRAIL-R2 and BCL2 expression levels, while metastatic EOC is associated with higher expression of these genes. Promoter DNA methylation was not related to this finding, suggesting there are other mechanisms involved in transcriptional control.
Literatur
1.
Zurück zum Zitat Bai M, Papoudou-Bai A, Horianopoulos N, Grepi C, Agnantis NJ, Kanavaros P (2007) Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin’s lymphomas. Hum Pathol 38:103–113PubMedCrossRef Bai M, Papoudou-Bai A, Horianopoulos N, Grepi C, Agnantis NJ, Kanavaros P (2007) Expression of bcl2 family proteins and active caspase 3 in classical Hodgkin’s lymphomas. Hum Pathol 38:103–113PubMedCrossRef
2.
Zurück zum Zitat Bast RC Jr, Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev 9:415–428CrossRef Bast RC Jr, Hennessy B, Mills GB (2009) The biology of ovarian cancer: new opportunities for translation. Nat Rev 9:415–428CrossRef
3.
Zurück zum Zitat Bevis KS, Buchsbaum DJ, Straughn JM Jr (2010) Overcoming TRAIL resistance in ovarian carcinoma. Gynecol Oncol 119:157–163PubMedCrossRef Bevis KS, Buchsbaum DJ, Straughn JM Jr (2010) Overcoming TRAIL resistance in ovarian carcinoma. Gynecol Oncol 119:157–163PubMedCrossRef
4.
Zurück zum Zitat Braga L, Ramos A, Traiman P, Silva L, Silva-Filho A (2012) TRAIL-R3-related apoptosis: epigenetic and expression analyses in women with ovarian neoplasia. Gynecol Oncol 126:268–273CrossRef Braga L, Ramos A, Traiman P, Silva L, Silva-Filho A (2012) TRAIL-R3-related apoptosis: epigenetic and expression analyses in women with ovarian neoplasia. Gynecol Oncol 126:268–273CrossRef
5.
Zurück zum Zitat Bras M, Queenan B, Susin SA (2005) Programmed cell death via mitochondria: different modes of dying. Biochemistry 70:231–239PubMed Bras M, Queenan B, Susin SA (2005) Programmed cell death via mitochondria: different modes of dying. Biochemistry 70:231–239PubMed
6.
Zurück zum Zitat Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966PubMedCrossRef Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23:2950–2966PubMedCrossRef
7.
Zurück zum Zitat Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG (1997) The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7:813–820PubMedCrossRef Degli-Esposti MA, Dougall WC, Smolak PJ, Waugh JY, Smith CA, Goodwin RG (1997) The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. Immunity 7:813–820PubMedCrossRef
8.
Zurück zum Zitat Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186:1165–1170PubMedCentralPubMedCrossRef Degli-Esposti MA, Smolak PJ, Walczak H, Waugh J, Huang CP, DuBose RF, Goodwin RG, Smith CA (1997) Cloning and characterization of TRAIL-R3, a novel member of the emerging TRAIL receptor family. J Exp Med 186:1165–1170PubMedCentralPubMedCrossRef
9.
Zurück zum Zitat Elias A, Siegelin MD, Steinmuller A, von Deimling A, Lass U, Korn B, Mueller W (2009) Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin Cancer Res 15:5457–5465PubMedCrossRef Elias A, Siegelin MD, Steinmuller A, von Deimling A, Lass U, Korn B, Mueller W (2009) Epigenetic silencing of death receptor 4 mediates tumor necrosis factor-related apoptosis-inducing ligand resistance in gliomas. Clin Cancer Res 15:5457–5465PubMedCrossRef
11.
Zurück zum Zitat Elrod HA, Fan S, Muller S, Chen GZ, Pan L, Tighiouart M, Shin DM, Khuri FR, Sun SY (2010) Analysis of death receptor 5 and caspase-8 expression in primary and metastatic head and neck squamous cell carcinoma and their prognostic impact. PLoS One 5:e12178PubMedCentralPubMedCrossRef Elrod HA, Fan S, Muller S, Chen GZ, Pan L, Tighiouart M, Shin DM, Khuri FR, Sun SY (2010) Analysis of death receptor 5 and caspase-8 expression in primary and metastatic head and neck squamous cell carcinoma and their prognostic impact. PLoS One 5:e12178PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Falschlehner C, Emmerich CH, Gerlach B, Walczak H (2007) TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 39:1462–1475PubMedCrossRef Falschlehner C, Emmerich CH, Gerlach B, Walczak H (2007) TRAIL signalling: decisions between life and death. Int J Biochem Cell Biol 39:1462–1475PubMedCrossRef
13.
Zurück zum Zitat Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S (2005) Role of mitochondria in toxic oxidative stress. Mol Interv 5:94–111PubMedCrossRef Fariss MW, Chan CB, Patel M, Van Houten B, Orrenius S (2005) Role of mitochondria in toxic oxidative stress. Mol Interv 5:94–111PubMedCrossRef
14.
Zurück zum Zitat FIGO IFoGaO (2009) Clinical practice guidelines FIGO IFoGaO (2009) Clinical practice guidelines
15.
Zurück zum Zitat Frankel A, Rosen K, Filmus J, Kerbel RS (2001) Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X(L). Cancer Res 61:4837–4841PubMed Frankel A, Rosen K, Filmus J, Kerbel RS (2001) Induction of anoikis and suppression of human ovarian tumor growth in vivo by down-regulation of Bcl-X(L). Cancer Res 61:4837–4841PubMed
16.
Zurück zum Zitat Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25:4798–4811PubMedCrossRef Fulda S, Debatin KM (2006) Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25:4798–4811PubMedCrossRef
17.
Zurück zum Zitat Gronbaek KHC, Jones PA (2007) Epigenetic changes in cancer. APMIS 115:10CrossRef Gronbaek KHC, Jones PA (2007) Epigenetic changes in cancer. APMIS 115:10CrossRef
18.
Zurück zum Zitat Hausmann M, Leucht K, Ploner C, Kiessling S, Villunger A, Becker H, Hofmann C, Falk W, Krebs M, Kellermeier S, Fried M, Scholmerich J, Obermeier F, Rogler G (2011) BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. J Biol Chem 286:26533–26540PubMedCentralPubMedCrossRef Hausmann M, Leucht K, Ploner C, Kiessling S, Villunger A, Becker H, Hofmann C, Falk W, Krebs M, Kellermeier S, Fried M, Scholmerich J, Obermeier F, Rogler G (2011) BCL-2 modifying factor (BMF) is a central regulator of anoikis in human intestinal epithelial cells. J Biol Chem 286:26533–26540PubMedCentralPubMedCrossRef
20.
Zurück zum Zitat Hennessy BT, Murph M, Nanjundan M, Carey M, Auersperg N, Almeida J, Coombes KR, Liu J, Lu Y, Gray JW, Mills GB (2008) Ovarian cancer: linking genomics to new target discovery and molecular markers: the way ahead. Adv Exp Med Biol 617:23–40PubMedCentralPubMedCrossRef Hennessy BT, Murph M, Nanjundan M, Carey M, Auersperg N, Almeida J, Coombes KR, Liu J, Lu Y, Gray JW, Mills GB (2008) Ovarian cancer: linking genomics to new target discovery and molecular markers: the way ahead. Adv Exp Med Biol 617:23–40PubMedCentralPubMedCrossRef
21.
Zurück zum Zitat Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCentralPubMedCrossRef Herman JG, Graff JR, Myohanen S, Nelkin BD, Baylin SB (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci USA 93:9821–9826PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Hopkins-Donaldson S, Ziegler A, Kurtz S, Bigosch C, Kandioler D, Ludwig C, Zangemeister-Wittke U, Stahel R (2003) Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ 10:356–364PubMedCrossRef Hopkins-Donaldson S, Ziegler A, Kurtz S, Bigosch C, Kandioler D, Ludwig C, Zangemeister-Wittke U, Stahel R (2003) Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ 10:356–364PubMedCrossRef
23.
Zurück zum Zitat Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277–288PubMedCrossRef Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277–288PubMedCrossRef
24.
Zurück zum Zitat Imura M, Yamashita S, Cai LY, Furuta J, Wakabayashi M, Yasugi T, Ushijima T (2006) Methylation and expression analysis of 15 genes and three normally-methylated genes in 13 ovarian cancer cell lines. Cancer Lett 241:213–220PubMedCrossRef Imura M, Yamashita S, Cai LY, Furuta J, Wakabayashi M, Yasugi T, Ushijima T (2006) Methylation and expression analysis of 15 genes and three normally-methylated genes in 13 ovarian cancer cell lines. Cancer Lett 241:213–220PubMedCrossRef
25.
Zurück zum Zitat Jin Z, McDonald ER 3rd, Dicker DT, El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279:35829–35839PubMedCrossRef Jin Z, McDonald ER 3rd, Dicker DT, El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279:35829–35839PubMedCrossRef
26.
Zurück zum Zitat Kelly MM, Hoel BD, Voelkel-Johnson C (2002) Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Cancer Biol Ther 1:520–527PubMedCrossRef Kelly MM, Hoel BD, Voelkel-Johnson C (2002) Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Cancer Biol Ther 1:520–527PubMedCrossRef
27.
Zurück zum Zitat Khaider NG, Lane D, Matte I, Rancourt C, Piche A (2012) Targeted ovarian cancer treatment: the TRAILs of resistance. Am J Cancer Res 2:75–92PubMedCentralPubMed Khaider NG, Lane D, Matte I, Rancourt C, Piche A (2012) Targeted ovarian cancer treatment: the TRAILs of resistance. Am J Cancer Res 2:75–92PubMedCentralPubMed
28.
Zurück zum Zitat Kim K, Fisher MJ, Xu SQ, el-Deiry WS (2000) Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 6:335–346PubMed Kim K, Fisher MJ, Xu SQ, el-Deiry WS (2000) Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 6:335–346PubMed
29.
Zurück zum Zitat Lai JCWJ, Cheng YW, Yeh KT, Wu TC, Chen CY et al (2009) O6-methylguanine-DNA methyltransferase hypermethylation modulated by 17beta-estradiol in lung cancer cells. Anticancer Res 29:6 Lai JCWJ, Cheng YW, Yeh KT, Wu TC, Chen CY et al (2009) O6-methylguanine-DNA methyltransferase hypermethylation modulated by 17beta-estradiol in lung cancer cells. Anticancer Res 29:6
30.
Zurück zum Zitat Li YYF, Hua Y, Lu W, Xie X (2009) Identification of suitable reference genes for gene expression studies of human serous ovarian cancer by real-time polymerase chain reaction. Anal Biochem 394:7CrossRef Li YYF, Hua Y, Lu W, Xie X (2009) Identification of suitable reference genes for gene expression studies of human serous ovarian cancer by real-time polymerase chain reaction. Anal Biochem 394:7CrossRef
31.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2[−Delta Delta C(T)] method. Methods 25:402–408PubMedCrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2[−Delta Delta C(T)] method. Methods 25:402–408PubMedCrossRef
32.
Zurück zum Zitat Mahmood Z, Shukla Y (2010) Death receptors: targets for cancer therapy. Exp Cell Res 316:887–899PubMedCrossRef Mahmood Z, Shukla Y (2010) Death receptors: targets for cancer therapy. Exp Cell Res 316:887–899PubMedCrossRef
33.
Zurück zum Zitat Malhi H, Gores GJ (2006) TRAIL resistance results in cancer progression: a TRAIL to perdition? Oncogene 25:7333–7335PubMedCrossRef Malhi H, Gores GJ (2006) TRAIL resistance results in cancer progression: a TRAIL to perdition? Oncogene 25:7333–7335PubMedCrossRef
34.
Zurück zum Zitat Mellier G, Huang S, Shenoy K, Pervaiz S (2010) TRAILing death in cancer. Mol Asp Med 31:93–112CrossRef Mellier G, Huang S, Shenoy K, Pervaiz S (2010) TRAILing death in cancer. Mol Asp Med 31:93–112CrossRef
35.
Zurück zum Zitat Meng CFZX, Peng G, Dai DQ (2009) Promoter histone H3 lysine 9 di-methylation is associated with DNA methylation and aberrant expression of p16 in gastric cancer cells. Oncol Rep 22:7 Meng CFZX, Peng G, Dai DQ (2009) Promoter histone H3 lysine 9 di-methylation is associated with DNA methylation and aberrant expression of p16 in gastric cancer cells. Oncol Rep 22:7
36.
Zurück zum Zitat Min KJ, Jang JH, Lee JT, Choi KS, Kwon TK (2012) Glucocorticoid receptor antagonist sensitizes TRAIL-induced apoptosis in renal carcinoma cells through up-regulation of DR5 and down-regulation of c-FLIP(L) and Bcl-2. J Mol Med (Berl) 90:309–319CrossRef Min KJ, Jang JH, Lee JT, Choi KS, Kwon TK (2012) Glucocorticoid receptor antagonist sensitizes TRAIL-induced apoptosis in renal carcinoma cells through up-regulation of DR5 and down-regulation of c-FLIP(L) and Bcl-2. J Mol Med (Berl) 90:309–319CrossRef
37.
Zurück zum Zitat Nagaprashantha LD, Vatsyayan R, Lelsani PC, Awasthi S, Singhal SS (2011) The sensors and regulators of cell-matrix surveillance in anoikis resistance of tumors. Int J Cancer 128:743–752PubMedCentralPubMedCrossRef Nagaprashantha LD, Vatsyayan R, Lelsani PC, Awasthi S, Singhal SS (2011) The sensors and regulators of cell-matrix surveillance in anoikis resistance of tumors. Int J Cancer 128:743–752PubMedCentralPubMedCrossRef
38.
Zurück zum Zitat Ouellet V, Le Page C, Madore J, Guyot MC, Barres V, Lussier C, Tonin PN, Provencher DM, Mes-Masson AM (2007) An apoptotic molecular network identified by microarray: on the TRAIL to new insights in epithelial ovarian cancer. Cancer 110:297–308PubMedCrossRef Ouellet V, Le Page C, Madore J, Guyot MC, Barres V, Lussier C, Tonin PN, Provencher DM, Mes-Masson AM (2007) An apoptotic molecular network identified by microarray: on the TRAIL to new insights in epithelial ovarian cancer. Cancer 110:297–308PubMedCrossRef
39.
Zurück zum Zitat Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815–818PubMedCrossRef Pan G, Ni J, Wei YF, Yu G, Gentz R, Dixit VM (1997) An antagonist decoy receptor and a death domain-containing receptor for TRAIL. Science 277:815–818PubMedCrossRef
40.
Zurück zum Zitat Pavet V, Portal MM, Moulin JC, Herbrecht R, Gronemeyer H (2011) Towards novel paradigms for cancer therapy. Oncogene 30:1–20PubMedCrossRef Pavet V, Portal MM, Moulin JC, Herbrecht R, Gronemeyer H (2011) Towards novel paradigms for cancer therapy. Oncogene 30:1–20PubMedCrossRef
41.
Zurück zum Zitat Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821PubMedCrossRef Sheridan JP, Marsters SA, Pitti RM, Gurney A, Skubatch M, Baldwin D, Ramakrishnan L, Gray CL, Baker K, Wood WI, Goddard AD, Godowski P, Ashkenazi A (1997) Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. Science 277:818–821PubMedCrossRef
42.
Zurück zum Zitat Shivapurkar N, Toyooka S, Toyooka KO, Reddy J, Miyajima K, Suzuki M, Shigematsu H, Takahashi T, Parikh G, Pass HI, Chaudhary PM, Gazdar AF (2004) Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer 109:786–792PubMedCrossRef Shivapurkar N, Toyooka S, Toyooka KO, Reddy J, Miyajima K, Suzuki M, Shigematsu H, Takahashi T, Parikh G, Pass HI, Chaudhary PM, Gazdar AF (2004) Aberrant methylation of trail decoy receptor genes is frequent in multiple tumor types. Int J Cancer 109:786–792PubMedCrossRef
43.
Zurück zum Zitat Suzuki HGE, Chen W, Anbazhagan R, Van Engeland M, Weijenberg MP et al (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31:9CrossRef Suzuki HGE, Chen W, Anbazhagan R, Van Engeland M, Weijenberg MP et al (2002) A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer. Nat Genet 31:9CrossRef
44.
Zurück zum Zitat Taddei ML, Giannoni E, Fiaschi T, Chiarugi P (2012) Anoikis: an emerging hallmark in health and diseases. J Pathol 226:380–393PubMedCrossRef Taddei ML, Giannoni E, Fiaschi T, Chiarugi P (2012) Anoikis: an emerging hallmark in health and diseases. J Pathol 226:380–393PubMedCrossRef
45.
Zurück zum Zitat Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev 9:231–241CrossRef Taylor RC, Cullen SP, Martin SJ (2008) Apoptosis: controlled demolition at the cellular level. Nat Rev 9:231–241CrossRef
46.
Zurück zum Zitat Turker MS (2002) Gene silencing in mammalian cells and the spread of DNA methylation. Oncogene 21:5388–5393PubMedCrossRef Turker MS (2002) Gene silencing in mammalian cells and the spread of DNA methylation. Oncogene 21:5388–5393PubMedCrossRef
47.
Zurück zum Zitat van Noesel MM, van Bezouw S, Salomons GS, Voute PA, Pieters R, Baylin SB, Herman JG, Versteeg R (2002) Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. Cancer Res 62:2157–2161PubMed van Noesel MM, van Bezouw S, Salomons GS, Voute PA, Pieters R, Baylin SB, Herman JG, Versteeg R (2002) Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. Cancer Res 62:2157–2161PubMed
48.
Zurück zum Zitat Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16:5386–5397PubMedCentralPubMedCrossRef Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16:5386–5397PubMedCentralPubMedCrossRef
50.
Zurück zum Zitat Wu Y, Alvarez M, Slamon DJ, Koeffler P, Vadgama JV (2010) Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation. BMC Cancer. doi:10.1186/1471-2407-10-32 Wu Y, Alvarez M, Slamon DJ, Koeffler P, Vadgama JV (2010) Caspase 8 and maspin are downregulated in breast cancer cells due to CpG site promoter methylation. BMC Cancer. doi:10.​1186/​1471-2407-10-32
51.
Zurück zum Zitat Yap TA, Carden CP, Kaye SB (2009) Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev 9:167–181CrossRef Yap TA, Carden CP, Kaye SB (2009) Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev 9:167–181CrossRef
52.
Zurück zum Zitat Yerbes R, Palacios C, Lopez-Rivas A (2011) The therapeutic potential of TRAIL receptor signalling in cancer cells. Clin Transl Oncol 13:839–847PubMedCrossRef Yerbes R, Palacios C, Lopez-Rivas A (2011) The therapeutic potential of TRAIL receptor signalling in cancer cells. Clin Transl Oncol 13:839–847PubMedCrossRef
Metadaten
Titel
Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors
verfasst von
Letícia da Conceição Braga
Luciana Maria Silva
Josiane Barbosa Piedade
Paulo Traiman
Agnaldo Lopes da Silva Filho
Publikationsdatum
01.05.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 5/2014
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-013-3060-0

Weitere Artikel der Ausgabe 5/2014

Archives of Gynecology and Obstetrics 5/2014 Zur Ausgabe

Hirsutismus bei PCOS: Laser- und Lichttherapien helfen

26.04.2024 Hirsutismus Nachrichten

Laser- und Lichtbehandlungen können bei Frauen mit polyzystischem Ovarialsyndrom (PCOS) den übermäßigen Haarwuchs verringern und das Wohlbefinden verbessern – bei alleiniger Anwendung oder in Kombination mit Medikamenten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

Bislang gibt es kein Medikament zur Prävention von Wochenbettdepressionen. Das Injektionsanästhetikum Esketamin könnte womöglich diese Lücke füllen.

Bei RSV-Impfung vor 60. Lebensjahr über Off-Label-Gebrauch aufklären!

22.04.2024 DGIM 2024 Kongressbericht

Durch die Häufung nach der COVID-19-Pandemie sind Infektionen mit dem Respiratorischen Synzytial-Virus (RSV) in den Fokus gerückt. Fachgesellschaften empfehlen eine Impfung inzwischen nicht nur für Säuglinge und Kleinkinder.

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.