title: High circulating estrogens and selective expression of ERβ in prostate tumors of Americans: implications for racial disparity of prostate cancer.
abstract: Although estrogen receptor beta (ERβ) has been implicated in prostate cancer (PCa) progression, its potential role in health disparity of PCa remains elusive. The objective of this study was to examine serum estrogens and prostate tumor ERβ expression and examine their correlation with clinical and pathological parameters in African American (AA) versus Caucasian American (CA) men. The circulating 17β-estradiol (E2) was measured by enzyme immunoassay in blood procured from racially stratified normal subjects and PCa patients. Differential expression profile analysis of ERβ was analyzed by quantitative immunohistochemistry using ethnicity-based tissue microarray encompassing 300 PCa tissue cores. In situ ERβ expression was validated by quantitative reverse transcription-PCR in matched microdissected normal prostate epithelium and tumor cells and datasets extracted from independent cohorts. In comparison with normal age-matched subjects, circulating E2 levels were significantly elevated in all PCa patients. Further analysis demonstrates an increase in blood E2 levels in AA men in both normal and PCa in comparison with age- and stage-matched counterparts of CA decent. Histochemical score analysis reveals intense nuclear immunoreactivity for ERβ in tumor cores of AA men than in CA men. Gene expression analysis in microdissected tumors corroborated the biracial differences in ERβ expression. Gene expression analysis from independent cohort datasets revealed correlation between ERβ expression and PCa progression. However, unlike in CA men, adjusted multivariate analysis showed that ERβ expression correlates with age at diagnosis and low prostate-specific antigen recurrence-free survival in AA men. Taken together, our results suggest that E2-ERβ axis may have potential clinical utility in PCa diagnosis and clinical outcome among AA men.
authors: Department of Urology.
authors: Zakaria Y
authors: ZY
authors: Abd Elmageed
authors: Krzysztof
authors: K
authors: Moroz
authors: Sudesh K
authors: SK
authors: Srivastav
authors: Zhide
authors: Z
authors: Fang
authors: Byron E
authors: BE
authors: Crawford
authors: Krishnarao
authors: K
authors: Moparty
authors: Raju
authors: R
authors: Thomas
authors: Asim B
authors: AB
authors: Abdel-Mageed
mesh_terms: D001741:Black or African American / Q000235:genetics; D004958:Estradiol / Q000097:blood*; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens / Q000097:blood*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis; D044465:White People / Q000235:genetics
chemical_list: D047629:Estrogen Receptor beta; D004967:Estrogens; D004958:Estradiol; D017430:Prostate-Specific Antigen
references: Ann N Y Acad Sci. 2006 Nov;1089:177-93
references: 17261766
references: Prostate. 2003 May 15;55(3):180-6
references: 12692783
references: Am J Pathol. 2001 Jul;159(1):79-92
references: 11438457
references: Endocr Relat Cancer. 2010 Jul 28;17(3):731-42
references: 20562232
references: J Clin Endocrinol Metab. 2007 Jul;92(7):2519-25
references: 17456570
references: J Cell Biochem. 2007 Nov 1;102(4):899-911
references: 17786930
references: Prostate. 2000 Oct 1;45(2):87-100
references: 11027407
references: Cancer Cell. 2010 Apr 13;17(4):319-32
references: 20385358
references: Mol Cell Endocrinol. 2003 Apr 28;202(1-2):201-7
references: 12770752
references: Eur J Cancer. 2003 Jun;39(9):1251-8
references: 12763213
references: Urology. 2004 Oct;64(4):814-20
references: 15491740
references: Arch Pathol Lab Med. 1985 Aug;109(8):716-21
references: 3893381
references: Ann Intern Med. 2002 Dec 3;137(11):917-29
references: 12458993
references: Altern Med Rev. 2002 Apr;7(2):112-29
references: 11991791
references: Clin Endocrinol (Oxf). 1993 Dec;39(6):649-55
references: 8287582
references: Endocrinology. 2006 Oct;147(10):4831-42
references: 16809442
references: Sci Signal. 2011 Apr 12;4(168):ra22
references: 21487105
references: Trends Pharmacol Sci. 2003 Sep;24(9):479-85
references: 12967773
references: J Cell Physiol. 2011 May;226(5):1334-9
references: 20945400
references: BMC Cancer. 2007 Apr 12;7:64
references: 17430594
references: J Biol Chem. 2002 Jul 5;277(27):24353-60
references: 11986316
references: Sci Signal. 2011 Apr 12;4(168):pe19
references: 21487104
references: Cancer Cell. 2010 Jul 13;18(1):11-22
references: 20579941
references: Cancer Res. 2002 Sep 15;62(18):5365-9
references: 12235008
references: J Clin Endocrinol Metab. 2001 May;86(5):2051-5
references: 11344205
references: Endocr Rev. 1999 Jun;20(3):358-417
references: 10368776
references: Biostatistics. 2003 Apr;4(2):249-64
references: 12925520
references: Prostate. 2002 Jun 1;52(1):69-81
references: 11992621
references: J Biol Chem. 2002 Sep 6;277(36):32510-5
references: 12084714
references: Prostate. 2003 Feb 1;54(2):79-87
references: 12497580
references: Gynecol Oncol. 2009 Mar;112(3):537-42
references: 19108875
references: Endocrinology. 1997 Mar;138(3):863-70
references: 9048584
references: Cancer Causes Control. 2006 Dec;17(10):1237-44
references: 17111254
references: Endocrinology. 2011 Jun;152(6):2150-63
references: 21427218
references: Cancer Epidemiol Biomarkers Prev. 1993 Jan-Feb;2(1):27-32
references: 8420607
references: Cancer Res. 2000 Jun 15;60(12):3175-82
references: 10866308
references: Eur Urol. 2009 Mar;55(3):543-5
references: 19095344
references: J Urol. 2010 Nov;184(5):2172-8
references: 20850840
references: Curr Pharm Des. 2012;18(19):2734-57
references: 22390760
references: J Natl Cancer Inst Monogr. 2000;(27):39-66
references: 10963619
references: J Natl Cancer Inst. 2008 Feb 6;100(3):170-83
references: 18230794
references: J Clin Endocrinol Metab. 1993 Aug;77(2):375-81
references: 7688377
references: Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E573-84
references: 15536203
references: Cancer Res. 2000 Nov 1;60(21):6008-17
references: 11085521
references: Cancer Res. 2001 Mar 1;61(5):1919-26
references: 11280747