Augmentation of effects of interferon-stimulated genes by reversal of epigenetic silencing: potential application to melanoma.
Increased expression of genes, silenced by methylation of their promoters, could have relevance for increasing effects of not only interferons (IFNs) but also APO2L/TRAIL, cytotoxics and immunotherapeutics for melanoma and other malignancies. A resistant melanoma cell line, A375, lacked APO2L/TRAIL or apoptosis induction by either IFN-alpha2 or IFN-beta. However, apoptosis was induced by IFNs in A375 cells by 5-aza,2'-deoxycytidine (5-Aza-dC), evaluated based upon the postulate that promoter methylation might be silencing pro-apopoptotic IFN-stimulated genes (ISGs). RASSF1A, commonly methylated at high frequency in many tumors including melanoma, which we discovered to be also an IFN-regulated gene, was increased by 5-Aza-dC. RASSF1A was important in enhancing apoptotic effects of not only IFNs and APO2L/TRAIL but also cisplatin. Unraveling epigenetic regulatory mechanisms, as yet only partially identified, will result in new biological insights and improved strategies for therapeutic use of IFNs or ISGs such as APO2L/TRAIL.
Borden
Ernest C
EC
Taussig Cancer Center and Case Comprehensive Cancer Center, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, United States. bordene@ccf.org
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
D000998:Antiviral Agents; D007372:Interferons
Cancer Res. 1993 May 15;53(10 Suppl):2410-5
7683574
Cancer Res. 1994 Mar 15;54(6):1422-4
8137242
Oncogene. 1994 May;9(5):1361-5
8152796
Cancer Res. 1994 Apr 15;54(8):2060-3
7513608
J Natl Cancer Inst. 1995 Feb 15;87(4):257-64
7535860
Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):211-5
8552607
Cancer Invest. 1996;14(1):25-53
8597888
Nat Genet. 2004 Feb;36(2):117-8
14752520
Nat Cell Biol. 2004 Feb;6(2):129-37
14743218
J Interferon Cytokine Res. 2003 Dec;23(12):745-56
14769151
Gut. 2004 Mar;53(3):425-30
14960528
Annu Rev Biochem. 1998;67:227-64
9759489
Blood. 1999 Jun 15;93(12):4347-53
10361133
Cancer Res. 2004 Nov 1;64(21):8109-15
15520223
Semin Hematol. 2005 Jul;42(3 Suppl 2):S3-8
16015502
J Interferon Cytokine Res. 2005 Sep;25(9):511-27
16181052
J Leukoc Biol. 2005 Oct;78(4):898-908
16037410
Cancer Res. 2006 Jan 15;66(2):653-8
16423993
Mol Cell Biol. 2006 Mar;26(5):1888-97
16479007
Cancer Res. 2006 Mar 1;66(5):2785-93
16510600
J Leukoc Biol. 2006 Jun;79(6):1286-94
16624932
Carcinogenesis. 2006 Jul;27(7):1341-8
16501252
Cancer Res. 2006 Jul 1;66(13):6692-8
16818643
Immunology. 2006 Jul;118(3):302-10
16827891
J Clin Oncol. 2006 Aug 10;24(23):3771-9
16801630
Clin Cancer Res. 2006 Aug 1;12(15):4619-27
16899610
J Natl Compr Canc Netw. 2006 Sep;4(8):751-7
16948953
Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14007-12
10570189
Leukemia. 1999 Dec;13(12):1960-71
10602416
Nat Genet. 2000 Mar;24(3):227-35
10700174
J Immunol. 2000 Apr 15;164(8):4143-9
10754309
Nat Genet. 2000 Jul;25(3):315-9
10888881
Oncogene. 2000 Jul 13;19(30):3372-83
10918594
Bone Marrow Transplant. 2000 May;25 Suppl 2:S88-95
10933198
Semin Cancer Biol. 2000 Apr;10(2):73-81
10936058
J Biol Chem. 2000 Oct 13;275(41):31805-12
10924517
Genomics. 2000 Nov 15;70(1):113-22
11087668
J Biol Chem. 2000 Nov 17;275(46):35669-72
10998413
Nat Cell Biol. 2001 Feb;3(2):128-33
11175744
Cancer Res. 2001 Apr 15;61(8):3225-9
11309270
Clin Cancer Res. 2001 Jun;7(6):1821-31
11410525
Blood. 2001 Oct 1;98(7):2183-92
11568006
Nat Genet. 2002 Feb;30(2):181-4
11799394
Dig Dis Sci. 2002 Jan;47(1):170-6
11837720
Oncogene. 2002 Feb 14;21(8):1251-62
11850845
Cancer Res. 2002 Feb 15;62(4):961-6
11861364
Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2830-5
11880635
Hematol J. 2000;1(1):7-14
11920164
Nature. 2002 Apr 4;416(6880):552-6
11932749
Br J Surg. 2002 Apr;89(4):418-22
11952580
Mol Cell Biol. 2002 Jun;22(12):4309-18
12024041
Nat Rev Genet. 2002 Jun;3(6):415-28
12042769
J Clin Oncol. 1996 Oct;14(10):2666-73
8874325
J Immunol. 1996 Nov 1;157(9):4100-8
8892645
Cell Growth Differ. 1997 Mar;8(3):343-52
9056677
J Clin Oncol. 1997 Jun;15(6):2351-8
9196150
Oncogene. 1997 Jul 24;15(4):453-7
9242382
Semin Oncol. 1998 Feb;25(1 Suppl 1):3-8
9482534
Cancer Res. 1998 Jun 15;58(12):2489-99
9635566
Cancer Res. 1998 Aug 15;58(16):3660-7
9721876
J Mol Biol. 1998 Sep 25;282(3):585-99
9737924
Oncology (Williston Park). 2004 Oct;18(11):1443-50; discussion 1457-9
15609471
J Invest Dermatol. 2004 Dec;123(6):1127-34
15610524
Leuk Res. 2005 Mar;29(3):283-6
15661263
Clin Exp Immunol. 2005 Mar;139(3):468-75
15730392
Annu Rev Pharmacol Toxicol. 2005;45:629-56
15822191
Cancer Res. 2005 May 1;65(9):3497-508
15867337
Nat Immunol. 2005 Jul;6(7):722-9
15951814
Cancer Biol Ther. 2003 Sep-Oct;2(5):552-6
14614325
N Engl J Med. 2003 Nov 20;349(21):2042-54
14627790
Ann Surg Oncol. 2003 Dec;10(10):1184-90
14654475
Semin Oncol. 2002 Jun;29(3 Suppl 7):18-26
12068384
J Immunol. 2002 Jul 15;169(2):847-55
12097388
Cleve Clin J Med. 2002 Jul;69(7):529, 533-4, 536-8 passim
12109636
J Biol Chem. 2002 Aug 9;277(32):28504-11
12029096
Int Immunol. 2002 Oct;14(10):1225-31
12356687
Clin Exp Metastasis. 2002;19(6):541-50
12405292
J Immunol. 2002 Nov 15;169(10):5978-85
12421984
Nat Genet. 2002 Dec;32(4):581-3
12415269
Nat Genet. 2003 Jan;33(1):61-5
12496760
Cancer Chemother Pharmacol. 2003 Mar;51(3):231-9
12655442
Cancer Res. 2003 Apr 1;63(7):1639-43
12670917
Tissue Antigens. 2003 Mar;61(3):211-9
12694570
Cell Death Differ. 2003 Mar;10(3):356-64
12700635
Clin Cancer Res. 2003 May;9(5):1721-7
12738726
Apoptosis. 2003 Jun;8(3):237-49
12766484
Oncogene. 2003 Jun 26;22(26):4118-27
12821946
Anticancer Res. 2003 May-Jun;23(3A):2043-51
12894577
Cancer Invest. 2003 Jun;21(3):394-9
12901286
Cancer Res. 2003 Nov 1;63(21):7068-75
14612497
Carcinogenesis. 2004 Mar;25(3):389-97
14633663
Clin Cancer Res. 2004 Mar 1;10(5):1670-7
15014018
Cancer Res. 2004 May 1;64(9):3137-43
15126351
Oncogene. 2004 May 13;23(22):4014-22
15064737
Int J Oncol. 2004 Aug;25(2):419-27
15254740
Cell Death Differ. 2004 Aug;11(8):915-23
15118763
Cancer Res. 2004 Aug 1;64(15):5270-82
15289333
N Engl J Med. 2004 Sep 2;351(10):998-1012
15342808
Cancer Res. 1982 Dec;42(12):4948-53
7139598
Cancer Res. 1985 Feb;45(2):863-71
3881175
J Interferon Res. 1986 Jun;6(3):189-98
3745984
J Interferon Res. 1986 Dec;6(6):615-25
2437222
Immunogenetics. 1987;26(1-2):92-8
2440802
Clin Exp Immunol. 1987 Jul;69(1):107-15
3652526
J Natl Cancer Inst. 1988 Apr 6;80(3):148-9
2450206
J Leukoc Biol. 1989 Jan;45(1):29-34
2463322
J Natl Cancer Inst. 1989 Jul 19;81(14):1061-8
2472488
N Engl J Med. 1990 Jan 11;322(2):77-82
2294436
Cancer Res. 1990 Feb 15;50(4):1071-4
2297754
J Interferon Res. 1990 Apr;10(2):141-51
2140395
J Biol Response Mod. 1990 Aug;9(4):368-77
2395002
Cancer Res. 1991 Mar 15;51(6):1684-8
1998958
Cancer Res. 1991 Aug 15;51(16):4155-63
1907881
J Interferon Res. 1992 Apr;12(2):131-7
1374455
J Natl Cancer Inst. 1992 Aug 5;84(15):1185-90
1378904
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10557-61
1438246