title: Combination effects of dietary soy and methylselenocysteine in a mouse model of prostate cancer.
abstract: BACKGROUND
  High dietary intake of soy or selenium (Se) is associated with decreased risk of prostate cancer. Soy constituents and various chemical forms of Se have each been shown to downregulate expression of the androgen receptor (AR) and AR-regulated genes in the prostate. We hypothesized that downregulation of AR and AR-regulated genes by the combination of these dietary components would inhibit tumorigenesis in the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse.
  
  
  METHODS
  Male mice were exposed from conception to stock diets high or low in soy, with or without a supplement of Se-methylseleno-L-cysteine (MSC) in a 2 × 2 factorial design. Mice were sacrificed at 18 weeks. Prostate histopathology, urogenital tract (UGT) weight, hepatic activity of androgen-metabolizing enzymes, and expression of AR, AR-regulated, and AR-associated FOX family genes, in the dorsolateral prostate were examined.
  
  
  RESULTS
  High soy intake decreased activity of hepatic aromatase and 5α-reductase, expression of AR, AR-regulated genes, FOXA1, UGT weight, and tumor progression, and upregulated protective FOXO3. Supplemental MSC upregulated AKR1C14, which reduces 5α-dihydrotestosterone.
  
  
  CONCLUSIONS
  Soy is an effective pleiotropic dietary agent for prevention of prostate cancer. The finding of effects of soy on FOX family gene expression in animals is novel. Combination effects of supplemental MSC may depend upon the soy content of the basal diet to which it is added.
authors: Department of Nutrition, Dietetics, and Food Science, Brigham Young University, Provo, Utah 84602, USA. merrill_christensen@byu.edu
authors: Merrill J
authors: MJ
authors: Christensen
authors: Trevor E
authors: TE
authors: Quiner
authors: Heather L
authors: HL
authors: Nakken
authors: Edwin D
authors: ED
authors: Lephart
authors: Dennis L
authors: DL
authors: Eggett
authors: Paul M
authors: PM
authors: Urie
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000178:diet therapy / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D017279:Selenocysteine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D045730:Soy Foods
chemical_list: D011944:Receptors, Androgen; D017279:Selenocysteine; C002979:selenomethylselenocysteine
references: J Nutr. 1993 Nov;123(11):1939-51
references: 8229312
references: J Pathol. 2012 Jul;227(3):286-97
references: 22553170
references: CA Cancer J Clin. 2012 Jan-Feb;62(1):10-29
references: 22237781
references: J Nutr Biochem. 1995 Jul;6(7):367-372
references: 12049997
references: Cancer Genomics Proteomics. 2005 Apr;2(2):97-114
references: 18548127
references: Prostate Cancer Prostatic Dis. 1999 Mar;2(2):70-75
references: 12496841
references: Cancer Prev Res (Phila). 2010 Aug;3(8):994-1006
references: 20647336
references: Mol Cancer. 2009 Dec 14;8:121
references: 20003443
references: Cancer Res. 2009 Apr 15;69(8):3695-703
references: 19351854
references: Cancer Prev Res (Phila). 2009 May;2(5):484-95
references: 19401524
references: Lab Invest. 2008 Oct;88(10):1049-56
references: 18762779
references: Int J Oncol. 2011 Aug;39(2):301-9
references: 21567081
references: Cell. 2011 Mar 4;144(5):646-74
references: 21376230
references: Curr Cancer Drug Targets. 2010 Mar;10(2):135-46
references: 20088800
references: Cochrane Database Syst Rev. 2011 May 11;(5):CD005195
references: 21563143
references: BMC Cancer. 2010 Aug 10;10:418
references: 20698994
references: Curr Drug Targets. 2003 Apr;4(3):231-41
references: 12643473
references: Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2193-203
references: 18006906
references: Biochem Biophys Res Commun. 1994 Jul 15;202(1):271-7
references: 7518676
references: Front Neuroendocrinol. 2009 Jul;30(2):119-29
references: 19351544
references: J Endocrinol. 2012 Feb;212(2):199-205
references: 22128327
references: J Carcinog. 2007 Mar 16;6:3
references: 17367528
references: BJU Int. 2003 May;91(7):608-12
references: 12699469
references: Clin Exp Metastasis. 2010 Oct;27(7):465-80
references: 20517637
references: Minerva Endocrinol. 2006 Mar;31(1):1-12
references: 16498360
references: Am J Hum Genet. 2001 Oct;69(4):685-94
references: 11519011
references: Am J Pathol. 2008 Jan;172(1):236-46
references: 18156212
references: JAMA. 2009 Jan 7;301(1):39-51
references: 19066370
references: BMC Med. 2011 Sep 15;9:105
references: 21920036
references: Lab Invest. 2000 Nov;80(11):1657-70
references: 11092526
references: BJU Int. 2009 Jun;103(11):1574-80
references: 19220249
references: Prostate. 2006 Jul 1;66(10):1070-5
references: 16637076
references: J Cancer Sci Ther. 2012;2011(S3):
references: 22422102
references: Reprod Biol Endocrinol. 2004 Jan 16;2:5
references: 14728729
references: J Nutr. 2011 Dec;141(12):2159-65
references: 22031663
references: Proc Soc Exp Biol Med. 1999 Jun;221(2):131-5
references: 10352124
references: Cancer Prev Res (Phila). 2010 May;3(5):576-8
references: 20424133
references: Front Biosci (Elite Ed). 2012 Jan 01;4:410-25
references: 22201883
references: Nutr Cancer. 2009;61(5):598-606
references: 19838933
references: Mol Endocrinol. 2009 Feb;23(2):213-25
references: 19074551
references: Reprod Biol Endocrinol. 2008 Nov 24;6:57
references: 19025659
references: Am J Pathol. 2012 Feb;180(2):848-61
references: 22138582
references: Nutr Cancer. 2011;63(5):778-89
references: 21614726
references: Toxicol Pathol. 2003 Jan-Feb;31(1):31-8
references: 12597447
references: PLoS One. 2010 Apr 29;5(4):e10423
references: 20454690
references: J Urol. 2011 May;185(5):1894-8
references: 21421236
references: Endocr Relat Cancer. 2010 Jan 29;17(1):R39-52
references: 19926708
references: Clin Cancer Res. 2009 Feb 1;15(3):752-7
references: 19188143