This document reviews literature on the expression of genes involved in sex steroid hormone metabolism and activity in normal, benign, and cancerous prostate tissues. It aims to determine if there is an association between gene expression and factors like age, BMI, and estrogen and testosterone levels. The literature search found articles studying expression of genes like the androgen receptor and enzymes involved in androgen and estrogen metabolism using techniques including immunohistochemistry, microarrays, and real-time PCR. Understanding epigenetic regulation of these genes may provide insights into prostate carcinogenesis.

1. A Review of the Expression of Genes Involved in Sex Steroid Hormone
Metabolism and Activity in Prostate Tissue: A Need for Epigenetic
Information
Jamie Ritchey1, MPH; Wilfried Karmaus1, MD, Dr.med, MPH; Tara Sabo-Attwood1,2, PhD; Susan E. Steck1,3, PhD, MPH, RD; Hongmei Zhang1, PhD;
1Department of Epidemiology and Biostatistics, 2Department of Environmental Health Sciences, 3Cancer Prevention and Control Program, University of South
Carolina, 800 Sumter Street, Columbia, SC 29208.
OBJECTIVE RESULTS
• To review the literature for gene expression of Figure 1. A plausible gene expression network
enzymes and receptors involved in sex steroid Table 1. Literature search summary
hormone metabolism and activity in normal, benign,
for genes and receptors involved in Estrogen (E)
and cancerous prostate tissues and Testosterone (T) metabolism in the prostate Gene &
Chromosomal location
Total articles
retrieved
Laboratory
methods†
[3, 11, 19-20] Androgen Metabolism
AR 26 IHC, Microarrays, IS, ISV, real-time PCR
Ch Xq12
• To determine if there is an association with gene HSD17B2
Ch 16q24.1-q24.2
4 IHC, ISH, Microarray, real-time PCR
expression and age, body mass index, estrogen and HSD17B3
Ch 9q22
4 IHC, microarray, real-time PCR
testosterone levels, and cancer treatments SRD5A1
Ch 5p15.31
6 IHC, ISH, Microarray
SRD5A2 10 IHC, ISH, Microarray, real-time PCR
Ch 2p23.1
INTRODUCTION CYP3A4
Ch 7q21.1-22
CYP3A5
5
6
IHC, real-time PCR
IHC, real-time PCR, meta-analysis
• Age, race, and family history are the only confirmed Ch 7q21.1-22
CYP3A7 3 IHC, real-time PCR
risk factors for prostate cancer [1]
Ch 7q21.1-22
CYP3A43 1 ICH, real-time PCR
Ch 7q21.1
AKR1C3 6 Array, real-time PCR, Northern blot, review
Ch 10p15-14
• Observational, clinical, and laboratory evidence AKR1C2
Ch 10p15-14
5 Array, real-time PCR, review
indicate that sex steroid hormones are important to HSD3B1
Ch 1p13-11
2 Array, real-time PCR
the development and progression of prostate cancer
HSD3B2 3 Array, review
Ch 1p13.1
UGT2B15 3 Array, microarray
[2-14] Ch 4q13
UGT2B17 3 IHC, ISH, real-time PCR
Ch 4q13
Estrogen Metabolism
• Epidemiology focusing on sex steroid hormone risk
ESR1 9 IHC, ISH, real-time PCR
Ch 6q24-27
ESR2 10 IHC, ISH, microarray, real-time PCR
and prostate cancer is inconclusive [2-14] Ch 14q31-22
CYP19A1 9 Avidin-biotin, IHC, ISH, microarray, real-time PCR
Ch 15q21
HSD17B1 2 IHC, real-time PCR
• Most epidemiologic studies have focused on gene
Ch 17q11-21
HSD17B4 5 IHC, ISH, microarray, real-time PCR, meta-analysis
Ch 5q2
single nucleotide polymorphisms (SNPs) of hormone HSD17B7
Ch 1q23
1 IHC
metabolic enzymes and serum hormone levels [2-3] SULT1A1
Ch 16p21.1
3 IHC, Western blot
SULT1A3 2 IHC, Western blot
RATIONALE
Ch 16p11.2
SULT2B1a 3 Northern blot, immunoblot, IHC
Ch 19 q13.3
• Gene expression may provide etiologic clues
SULT2Bb 3 Northern blot, immunoblot, IHC
Ch 19 q13.3
HSD17B12 1 IHC, ISH
regarding how sex steroid metabolism is associated Ch 11p11
CYP1A1 4 IHC, real-time PCR
with prostate cancer not detected at the DNA Ch 15q24.1
CYP1A2 4 IHC, real-time PCR
sequence or serum level [130]
Ch 15q24.1
CYP1B1 6 IHC, ISH, real-time PCR
Ch 2p22.2
COMT 2 IHC, real-time PCR
Ch 22q11.21
• The expression of genes involved in sex steroid GSTT1
Ch 22q11.23
1 Microarray, real-time PCR
metabolism in prostate tissues may differ by different
GSTM1 3 IHC, microarray, real-time PCR
Ch 1p13.1
GSTP1 10 IHC, IS, microarray, real-time PCR
levels of age, body mass index, race, estrogen and Ch 11q13.2
†Laboratory method abbreviations: Immunohistochemistry (IHC), Real-time polymerase chain reaction (real-time PCR), Immunostaining (IS), In situ
testosterone levels, and/or cancer treatments hybridization (ISH), Immunostaining with optimized IHC criteria and video image analysis (ISV)
administered • A total of 85 studies were identified
• To guide our searches, we constructed a figure of a
METHODS plausible gene network for E and T expression [3,11, • Most studies focused on the expression of one or
• A pathway-oriented approach guided the literature 19-20]. a few genes, rather than the complete pathway,
searches, conducted in Pub Med, limited to English
ignoring compensatory or alternate response
language and human prostate only • Past studies have only included portions of
pathways, or the T or E pathways alone, and often do • Studies comparing normal, benign, and cancerous
STRENGTHS not include preliminary pathways (the dashed line prostate tissue showed limited consistency, with
• Used a pathway approach to guide searches from androstenedione to DHT indicates that this one exception, the down-regulation of GSTP1 in
reaction is preliminary) [3,11,19-20]. cancerous tissue
• Omitted cell studies since results may not be
consistent with tissue studies for methodological
reasons
SUMMARY
• GSTP1 was consistently down regulated or not expressed in prostate cancer, which coincides with previous
• Reviewed references cited in publications found research indicating that GSTP1 is methylated in prostate cancer tissue [16,95,99-109,111-118,130,136]
during searches to improve completeness
• For all other genes, studies were either scant or inconsistent, and conflicting expression results may be due
LIMITATIONS to limitations, including: tissue collection, laboratory methods, or gene functionality
• Information for many genes was scant
• Few studies were found examining the association of gene expression with age, race, body mass index,
• Only publications in English language were estrogen, testosterone, and cancer treatments
considered
• Future studies should focus not only on gene expression, but also epigenetic mechanisms such as
• Only includes citations from PubMed methylation to assess prostate cancer risk
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