Association between an estrogen receptor alpha gene polymorphism and the risk of prostate cancer in black men

PURPOSE: Studies suggest that SNPs within ESR1 may be associated with an increased risk of prostate cancer. We evaluated the association of the XbaI and PvuII ESR1 SNPs and prostate cancer risk in 3 different racial/ethnic populations. MATERIALS AND METHODS: A total of 1,603 volunteers from the SABOR study (285 black, 876 white and 442 Hispanic men) were genotyped to assess allelic frequencies of the ESR1 SNPs. Case-control analysis was performed on 598 prostate cancer cases and 1,098 controls (260 black men, 1,013 non-Hispanic white men and 423 Hispanic white men) to assess the association between these polymorphisms and prostate cancer risk. RESULTS: Allelic frequency was significantly different across ethnic/racial groups for both SNPs. Logistic regression analysis adjusted for age and stratified by race and ethnicity demonstrated an association between the AG genotype or presence of the G allele (GG or AG genotype) in the XbaI SNP and prostate cancer risk within black men (OR 2.25, 95% CI 1.07-4.70, p = 0.031; OR 2.14, 95% CI 1.05-4.35, p = 0.035, respectively). No association was observed among Hispanic and non-Hispanic white men for this SNP. Furthermore, there was no association between the PvuII SNP and prostate cancer risk across all groups. CONCLUSIONS: Our study demonstrates an association between the AG genotype, as well as presence of the G allele within the XbaI ESR1 SNP and prostate cancer risk among black men.     

Ethnic and racial differences in prostate stromal estrogen receptor alpha

BACKGROUND: Prostate cancer incidence and mortality rates vary widely among individuals of different ethnic/racial groups. We identified a relationship between a subset of genes and race/ethnicity using gene expression profiling. Estrogen receptor alpha (ERalpha) was selected for confirmation due to its plausible biological role in cancer susceptibility. METHODS: Quantitative polymerase chain reaction (Q-PCR) was used to verify gene expression results. Protein levels of ERalpha were determined by quantitative immunohistochemistry in a large-scale tissue microarray study (n = 183). RESULTS: ERalpha was significantly higher in stroma of Hispanic and Asian men than in Caucasian (P < 0.0001) and African American men (P < 0.0002), who are at higher risk for prostate cancer. In addition, large differences were seen in Q-PCR levels of ERalpha in prostate tissues of organ donors 16-29 years old who had no evidence of cancer. CONCLUSIONS: ERalpha exhibits variable expression in men of difference racial/ethnic background. Understanding the molecular basis for these differences may form the basis for prostate cancer prevention strategies with widespread public health impact.     

Proliferation and phenotypic changes of stromal cells in response to varying estrogen/androgen levels in castrated rats

It is known that human benign prostatic hyperplasia might arise from an estrogen/androgen （E/T） imbalance. We studied the response of castrated rat prostate to different ratios of circulating E/T. The castrated male Wistar rats were randomly injected with E/T at different ratios for 4 weeks. The prostates of E/T （1：100） group showed a distinct prostatic hyperplasia response by prostatic index, hematoxylin and eosin staining, and quantitative immunohistochemical analysis of a-smooth muscle actin （SMA）. In this group, cells positive for Vimentin, non-muscle myosin heavy chain （NMMHC） and proliferating cell nuclear antigen （PCNA） increased in the stroma and epithelium. Furthermore, the mRNA levels of smooth muscle myosin heavy chain （SMMHC） and NMMHC increased. So E/T at a ratio of 1：100 can induce a stromal hyperplastic response in the prostate of castrated rats. The main change observed was an increase of smooth muscle cells, whereas some epithelial changes were also seen in the rat prostates.     

高胆固醇饮食对妊娠豚鼠胆囊AQPsmRNA及雌性激素受体的影响

目的 研究高胆固醇饮食对妊娠豚鼠胆囊运动及胆囊黏膜上皮水通道蛋白-1( AQP -1)和水通道蛋白-8(AQP -8)的影响.方法 60只妊娠豚鼠,随机分为实验组A组、B组和对照组,实验组给予致结石饮食(胆固醇含量分别为1％和0.5％)喂养8周.采用RT - PCR对其胆囊AQP -1与AQP -8进行检测,应用化学发...     

青春期乳房肥大症乳腺组织中雌激素受体的表达

目的:探讨雌激素受体(ER)在青春期乳房肥大症乳腺组织中的表达及意义.方法:应用免疫组化SP法检测了18例青春期乳房肥大症及1 2例原发性小乳症乳腺组织中ER的表达情况.结果:ER在青春期乳房肥大症和原发性小乳症乳腺组织中的阳性表达率分别为88.89%和16.67%,两者比较差异有统计学意义(P＜0.01).结论:青春期乳房肥大症的发生可能与乳腺组织中ER的表达增加有关.     

Roles of estrogen and SHBG in prostate physiology

Heretofore, the function of estrogen in the prostate, other than as an antiandrogen, has been unclear. In this review of a growing fund of knowledge about both estrogen and the plasma protein, sex hormone-binding globulin (SHBG), or testosterone-estradiol binding globulin (TeBG), the hypothesis is proposed that estrogen, mediated by SHBG, participates with androgen in setting the pace of prostatic growth and function. It is suggested that the estrogen not only directs stromal proliferation and secretion, but also, through IGF-I, conditions the response of the epithelium to androgen. © 1996 Wiley-Liss, Inc.     

Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease

BACKGROUND: Although up to 30% of men who undergo radical prostatectomy for clinically organ-confined prostate cancer will relapse with disseminated disease, currently it is not possible to predict these patients. METHODS: Androgen receptor (AR) immunoreactivity in stromal and epithelial compartments of tumor foci was evaluated by video image analysis in 53 radical prostatectomy specimens. Kaplan-Meier and Cox Regression analyses were used to determine whether AR immunostaining was related to rate and risk of relapse, respectively. RESULTS: Ninety-eight percent (52/53) of the tumors contained AR positive malignant epithelial cells. Kaplan-Meier analysis indicated that patients with high AR levels (>64% AR positive nuclear area) in the malignant epithelial cells or low AR levels (相似文献   

Changes in steroid receptors and proteoglycan expression in the guinea pig prostate stroma during puberty and hormone manipulation

BACKGROUND: Proteoglycans are structural and informational molecules important during embryogenesis and organ maturation. Maturation of the prostate is influenced by androgens and estrogens, but changes in the relative spatiotemporal expression of steroid receptors and proteoglycans during hormonal change are unexplored. METHODS: Guinea pig prostate was used to define hormone-induced changes in the expression of androgen (AR) and estrogen (ER(alpha)) receptors, chondroitin sulfate (CS) glycosaminoglycan and core proteins of versican and syndecan-1. Tissue locations of AR, ER(alpha), CS and the proteoglycans versican and syndecan-1 were determined by immunohistochemistry. Cellular content of ER(alpha) and syndecan-1 was assessed visually. Versican, CS56 epitope, and AR were quantified by image analysis. RESULTS: AR expression within prostate epithelial and stromal cell nuclei decreased following castration and increased following treatment of castrate animals with dihydrotestosterone (DHT). ER(alpha) expression was restricted to prostate stromal cell nuclei and decreased during puberty, and following treatment of castrate animals with DHT. Versican was present in periacinar stroma immediately peripheral to basal epithelial cells, fibromuscular stromal tissue bands surrounding acinar units, and loose fibrovascular connective tissue interspersed between individual acini. Versican and native CS expression decreased (>10-fold) in periacinar stroma during puberty and following administration of DHT to castrated animals. Expression of syndecan-1 was restricted to fibromuscular cells of prostate stroma, and remained constant during puberty and hormone manipulation. CONCLUSIONS: ER(alpha), versican core protein and CS side chain epitopes are negatively regulated in prostate stromal tissue by DHT, whilst AR levels are positively regulated.     

Expression of estrogen receptor alpha and progesterone receptor in children with undescended testicle previously treated with human chorionic gonadotropin

PURPOSE: The aim of this study was to investigate expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR) in paratesticular tissues obtained from boys with undescended testes. MATERIALS AND METHODS: A total of 65 boys with unilateral cryptorchidism and failed human chorionic gonadotropion treatment underwent orchiopexy. A small sample of gubernaculum, cremasteric muscle and processus vaginalis was obtained. A total of 57 boys who underwent inguinal hernia repair served as the control group. All boys in the control group had testes in the scrotum. The expression of estrogen receptor alpha and progesterone receptor was measured by counting the number of ERalpha or PR positive cells detected by immunohistochemical analysis. RESULTS: ERalpha and PR density was higher in cremasteric muscle and processus vaginalis obtained from boys with undescended testes than in the control group. Density of progesterone receptor in the examined groups was lower than the density of estrogen receptor. CONCLUSIONS: ERalpha and PR are expressed in paratesticular tissues important for normal testicular descent. ERalpha was over expressed in cremasteric muscle and processus vaginalis in boys with undescended testes previously treated with human chorionic gonadotropin.     

Role of androgen receptor in prostate cancer

The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80 % of prostate cancers initially respond to hormonal therapy, howcrver, more than half of the re-sponders gradtmlly become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnonnalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. “Ilais article focusedon the role of AR in the progression of prostate cancer.     

Steroid receptor profile in human prostate cancer metastases as compared with primary prostatic carcinoma

The steroid receptor profile in seven prostate cancer metastases was compared with the profile in seven primary prostate cancers. The secondaries were all lymph node metastases, obtained during pelvic lymphadenectomy, preceding radical prostatectomy or irradiation. Cytosol androgen receptor content was higher in metastases, whereas the nuclear androgen receptor content was only one-fourth that in primary cancer. Cytosol progesterone as well as estrogen receptor contents were markedly lower in metastases compared with primary cancer. The steroid receptor profile differed very little between primary cancer and normal tissue. Primary prostatic carcinoma is usually obtained at early stages of the disease, whereas metastases represent a dedifferentiated, more aggressive cell population. This may explain the low amounts of progesterone, estrogen, and nuclear androgen receptor levels. The total androgen receptor content was similar in metastatic and primary disease, however, with a shift towards a cytosolic predominance in metastases. Possibly androgen receptors in metastatic disease are "deactivated."     

Nuclear androgen receptors in the epithelium and stroma of human benign prostatic hypertrophic glands

Androgen receptors have been characterized and quantified in nuclear extracts of separated epithelium and stroma from human benign prostatic hypertrophic (BPH) glands. Tritiated dihydrotestosterone was used as the ligand and incubation was carried out at 15 degrees C for 18-20 hr before separation of bound and free ligand using dextran-coated charcoal. The results were analysed by Scatchard-type analysis. The concentration of receptor was found to be significantly (p = 0.022) greater in stromal than in epithelial nuclei: 1765 +/- 152 vs 1030 +/- 227 fmol/mg DNA (SEM, n = 6). Fourteen competitors were tested and the results indicated the presence of specific androgen receptors rather than contaminating sex-hormone-binding globulin. This was also borne out by the results of agar gel electrophoresis and sucrose gradient ultracentrifugation studies. The results are in line with current opinion that prostatic stroma is an important androgen-sensitive tissue, particularly in human BPH.     

Examination of the distribution of oestrogen receptor between the stromal and epithelial compartments of the canine prostate

The stromal and epithelial elements of the canine prostate gland have been mechanically separated for the individual measurement of the presence of oestrogen receptor. The purity of each fraction was assessed by light and electron microscopy and by certain biochemical parameters and was found to be good. The oestrogen receptor was demonstrated to be predominantly located in the stroma at a concentration of 181.5 ± 49.3 fmoles/mg cytosol protein compared with that in the epithelium of 44.5 ± 22.4 fmoles/mg cytosol protein. A high affinity for the tritiated ligand was also shown (kd = 2.81 ± 0.8) (× 10¹⁰). The significance of these findings is discussed, especially with regard to the development of prostatic hyperplasia.     

Understanding the role of estrogen in the development of benign prostatic hyperplasia

Introduction

Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate that affects ageing men. As the number of men affected by this condition will only continue to grow with the aging population, finding new strategies and new therapeutic options for its treatment is crucial. Androgenic hormones have been known to play an important role in the development of BPH and they have been a target in its medical treatment. Estrogens have also been implicated in BPH but in contrast to androgens, the functions of estrogens in the prostate are still obscure.