title: NF-κB signaling in prostate cancer: a promising therapeutic target?
abstract: Prostate carcinoma (PCa) displays a wide variety of genetic alterations, versatile expression profiles as well as cell surface markers. Despite this heterogeneity, a common treatment for advanced PCa is androgen deprivation therapy (ADT). ADT targets the androgen receptor-a member of the nuclear receptor superfamily-which is required for development and function of the prostate and critical for PCa growth and survival. After an initial regression of the tumor during ADT, a large fraction of tumors progress to so-called castration-resistant prostate carcinoma (CRPca) which is highly resistant toward chemotherapy. The ensuing high mortality rates illustrate the importance of novel therapeutic targets for CRPCa. The transcription factor NF-κB was recently proposed as such a potential target for therapeutic intervention in CRPCa. Although NF-κB is essential for the regulation of innate and adaptive immunity recent data suggest a role of NF-κB in cancer initiation and progression. However, the exact function of NF-κB signaling in PCa is still a matter of debate. Here, we review known roles of NF-κB signaling in PCa and emphasize the crosstalk of NF-κB and androgen receptor signaling. Finally, we discuss potential therapeutic relevance of blocking NF-κB in PCa.
authors.affiliation: Institute of Pathology, University of Ulm, Albert-Einstein-Allee 23, 89070, Ulm, Germany.
authors.forename: Garima
authors.initials: G
authors.lastname: Jain
authors.forename: Marcus V
authors.initials: MV
authors.lastname: Cronauer
authors.forename: Mark
authors.initials: M
authors.lastname: Schrader
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Ralf B
authors.initials: RB
authors.lastname: Marienfeld
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology*; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000503:physiopathology* / Q000601:surgery; D011944:Receptors, Androgen / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D017211:Treatment Failure
chemical_list: D059002:Androgen Receptor Antagonists; D016328:NF-kappa B; D011944:Receptors, Androgen
references.citation: Nat Med. 2000 Jun;6(6):703-6
references.pmid: 10835690
references.citation: Endocr Rev. 2007 Dec;28(7):778-808
references.pmid: 17940184
references.citation: Cancer Res. 2007 Jul 1;67(13):6263-9
references.pmid: 17616684
references.citation: Oncogene. 2006 Oct 30;25(51):6685-705
references.pmid: 17072322
references.citation: J Biol Chem. 2007 Mar 23;282(12):8724-33
references.pmid: 17244613
references.citation: Cell Signal. 2007 May;19(5):1093-100
references.pmid: 17292587
references.citation: Clin Chem. 1998 Apr;44(4):705-23
references.pmid: 9554481
references.citation: Cancer Res. 2006 Mar 1;66(5):2815-25
references.pmid: 16510604
references.citation: Clin Cancer Res. 2004 Aug 15;10(16):5501-7
references.pmid: 15328189
references.citation: Cancer Res. 2009 Dec 15;69(24):9448-56
references.pmid: 19934328
references.citation: J Clin Invest. 2005 Apr;115(4):849-59
references.pmid: 15776110
references.citation: Prostate. 2008 Dec 1;68(16):1725-33
references.pmid: 18781579
references.citation: Clin Cancer Res. 2009 May 15;15(10):3557-67
references.pmid: 19447876
references.citation: Curr Opin Urol. 2000 Sep;10(5):415-20
references.pmid: 11005445
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14477-82
references.pmid: 16973750
references.citation: Int J Oncol. 1997 Dec;11(6):1335-47
references.pmid: 21528343
references.citation: J Exp Clin Cancer Res. 2010 Dec 28;29:171
references.pmid: 21189143
references.citation: Cancer Lett. 2010 Sep 28;295(2):214-28
references.pmid: 20350779
references.citation: Cancer Res. 2010 Apr 15;70(8):3309-19
references.pmid: 20388792
references.citation: Endocr Relat Cancer. 2010 May 18;17(2):525-38
references.pmid: 20335309
references.citation: Cancer Res. 2008 Jun 1;68(11):4447-54
references.pmid: 18519708
references.citation: Am J Pathol. 2009 Aug;175(2):489-99
references.pmid: 19628766
references.citation: Clin Cancer Res. 2004 Apr 1;10(7):2466-72
references.pmid: 15073126
references.citation: Immunol Res. 2008;42(1-3):3-18
references.pmid: 18626576
references.citation: Clin Cancer Res. 2004 Dec 15;10(24):8460-4
references.pmid: 15623625
references.citation: J Immunol. 2004 Aug 1;173(3):1612-9
references.pmid: 15265889
references.citation: Oncogene. 2008 Sep 18;27(42):5635-42
references.pmid: 18504428
references.citation: Pancreas. 2008 Apr;36(3):225-35
references.pmid: 18362834
references.citation: Oncogene. 2006 Oct 30;25(51):6868-86
references.pmid: 17072333
references.citation: Nature. 2007 Apr 5;446(7136):690-4
references.pmid: 17377533
references.citation: Anticancer Res. 2010 Sep;30(9):3333-9
references.pmid: 20944105
references.citation: J Biol Chem. 1996 Sep 27;271(39):24151-6
references.pmid: 8798655
references.citation: Cell Res. 2008 Mar;18(3):334-42
references.pmid: 18301380
references.citation: Neoplasia. 2004 Jul-Aug;6(4):390-400
references.pmid: 15256061
references.citation: Mol Cell Biol. 1999 Aug;19(8):5785-99
references.pmid: 10409765
references.citation: Carcinogenesis. 2011 May;32(5):757-64
references.pmid: 21325633
references.citation: Prostate. 2002 Aug 1;52(3):183-200
references.pmid: 12111695
references.citation: Genes Dev. 2004 Sep 15;18(18):2195-224
references.pmid: 15371334
references.citation: Prostate. 2000 May 15;43(3):184-94
references.pmid: 10797493
references.citation: Nature. 2006 May 25;441(7092):431-6
references.pmid: 16724054
references.citation: Mol Cell Endocrinol. 2003 Mar 28;201(1-2):1-12
references.pmid: 12706288
references.citation: Oncogene. 2006 Jan 19;25(3):387-98
references.pmid: 16170348
references.citation: Nature. 2010 Mar 11;464(7286):302-5
references.pmid: 20220849
references.citation: Int J Cancer. 2007 Sep 1;121(5):999-1008
references.pmid: 17487836
references.citation: PLoS One. 2009;4(2):e4608
references.pmid: 19242540
references.citation: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7264-9
references.pmid: 16651533
references.citation: Cold Spring Harb Perspect Biol. 2009 Oct;1(4):a000034
references.pmid: 20066092
references.citation: Cancer Res. 2001 Jul 1;61(13):5038-44
references.pmid: 11431338
references.citation: Cancer Res. 2008 Aug 15;68(16):6762-9
references.pmid: 18701501
references.citation: J Biol Chem. 1995 Jan 13;270(2):837-42
references.pmid: 7822319
references.citation: J Biol Chem. 2003 May 30;278(22):19852-60
references.pmid: 12657634
references.citation: Cancer Res. 2001 May 1;61(9):3550-5
references.pmid: 11325816
references.citation: J Immunol. 2005 Nov 15;175(10):7021-8
references.pmid: 16272363
references.citation: J Biol Chem. 2008 Jan 4;283(1):76-86
references.pmid: 17977820