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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most frequently diagnosed cancer and a leading cause of cancer deaths in American men. High dietary intake and status of the essential trace element selenium (Se) have been consistently correlated with reduced risk for prostate cancer. One molecular mechanism by which Se may reduce prostate cancer risk is by catalyzing disulfide bond formation or, otherwise, complexing with reactive sulfhydryl groups in transcription factors, thus altering their binding to DNA and regulation of gene expression. Estrogen plays a role in the etiology of prostate cancer. Estrogen receptors contain cysteines in zinc fingers that are susceptible to oxidation and internal disulfide bond formation, which can prevent DNA binding. We hypothesized that Se alteration of estrogen receptor (ER) binding to DNA and estrogen-regulated gene expression may be one mechanism by which it exerts its chemopreventive effects. LNCaP human prostate cancer cells were treated with 0.05 mumol/L (control) or 5.0 mumol/L (high) Se as methylseleninic acid (MSA). Electrophoretic mobility shift assays showed that binding of ER-beta to the estrogen response element was a nonsignificant 14% lower in cells treated with high MSA. Run-on transcription assays showed no significant changes in transcription rates for estrogen-regulated genes, and steady-state mRNA levels for those genes, assayed by reverse transcription-polymerase chair reaction, were likewise unaffected by MSA. These results suggest that the well-documented chemopreventive effects of Se against prostate cancer may be mediated by mechanisms other than inhibition by monomethylated Se compounds of ER-beta activation or estrogen-regulated gene expression.
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PMID:Estrogen receptor activation and estrogen-regulated gene expression are unaffected by methylseleninic acid in LNCaP prostate cancer cells. 1743 22

In the present study, we demonstrate that Rosiglitazone (Rosi), a thiazolidinedione and PPARgamma agonist, induces ERE (Estrogen Receptor Response Element) reporter activity, pS2 (an endogenous ER gene target) expression, and proliferation of ER positive breast cancer (MCF-7) cells. By performing a dose-response assay, we determined that high concentrations of Rosi inhibit proliferation, while low concentrations of Rosi induce proliferation. Using the anti-estrogen ICI, ER negative breast cancer (MDA-MB-231) cells, and a prostate cancer cell line (22Rv1) deficient in both ERalpha and PPARgamma, we determined that Rosiglitazone-induced ERE reporter activation and proliferation is through an ERalpha dependent mechanism. Rosiglitazone-induced ERE activation is also dependent on activation of the Extracellular Signal-Regulated Kinase-Mitogen Activated Protein Kinase (ERK-MAPK) pathway, since it is inhibited by co-treatment with U0126, a specific inhibitor of this pathway. We also demonstrate that when ERalpha and PPARgamma are both present, they compete for Rosi, inhibiting each others transactivation. To begin to unravel the pharmacological mechanism of Rosi-induced ER activation, sub-maximally effective concentrations of E(2) were used in combination with increasing concentrations of Rosi in luciferase reporter assays. From these assays it appears that E(2) and Rosi both activate ERalpha via similar pharmacological mechanisms. Furthermore sub-maximally effective concentrations of E(2) and Rosi additively increase both ERE reporter activity and MCF-7 cell proliferation. The results of this study may have clinical relevancy for Rosi's use both as an anti-diabetic in post-menopausal women and as an anti-cancer drug in women with ER positive breast cancer.
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PMID:Transactivation of ERalpha by Rosiglitazone induces proliferation in breast cancer cells. 1745 34

Breast cancer is a hormone-dependent cancer like prostate cancer and endometrial cancer. Estrogen plays important roles in the development and progression of breast cancer. Endocrine therapy is the treatment of choice for estrogen receptor- and/or progesterone receptor-positive breast cancer. Endocrine therapy has been used for several purposes, including chemoprevention, preoperative treatment, postoperative adjuvant treatment and treatment for recurrent diseases. A large number of clinical trials have provided evidence showing the clinical benefits of various endocrine therapies for the treatment of breast cancer. The current status and recent advances in endocrine therapy for breast cancer are reviewed based on the results of current clinical trials. Future perspectives of endocrine therapy are also discussed.
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PMID:Current clinical trials of endocrine therapy for breast cancer. 1748 7

Previous studies suggest that enzymes involved in the androgen metabolic pathway are susceptibility factors for prostate cancer. Estrogen metabolites functioning as genotoxins have also been proposed as risk factors. In this study, we systematically tested the hypothesis that common genetic variations for those enzymes involved in the androgen and estrogen metabolic pathways increase risk for sporadic and familial prostate cancer. From these two pathways, 46 polymorphisms (34 single nucleotide polymorphisms, 10 short tandem repeat polymorphisms, and 2 null alleles) in 25 genes were tested for possible associations. Those genes tested included PRL, LHB, CYP11A1, HSD3B1, HSD3B2, HSD17B2, CYP17, SRD5A2, AKR1C3, UGT2B15, AR, SHBG, and KLK3 from the androgen pathway and CYP19, HSD17B1, CYP1A1, CYP1A2, CYP1B1, COMT, GSTP1, GSTT1, GSTM1, NQO1, ESR1, and ESR2 from the estrogen pathway. A case-control study design was used with two sets of cases: familial cases with a strong prostate cancer family history (n = 438 from 178 families) and sporadic cases with a negative prostate cancer family history (n = 499). The controls (n = 493) were derived from a population-based collection. Our results provide suggestive findings for an association with either familial or sporadic prostate cancer with polymorphisms in four genes: AKR1C3, HSD17B1, NQO1, and GSTT1. Additional suggestive findings for an association with clinical variables (disease stage, grade, and/or node status) were observed for single nucleotide polymorphisms in eight genes: HSD3B2, SRD5A2, SHBG, ESR1, CYP1A1, CYP1B1, GSTT1, and NQO1. However, none of the findings were statistically significant after appropriate corrections for multiple comparisons. Given that the point estimates for the odds ratio for each of these polymorphisms are <2.0, much larger sample sizes will be required for confirmation.
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PMID:Evaluation of genetic variations in the androgen and estrogen metabolic pathways as risk factors for sporadic and familial prostate cancer. 1750 24

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR, alone and in combination, point to a favorable outcome for patients with OC.
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PMID:Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study. 1791 54

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.
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PMID:Haplotypes of the estrogen receptor beta gene and breast cancer risk. 1793 38

The male breast cancer accounts for nearly 1% of all breast cancer cases and bilateral involvement occurs in less than 2% of the cases. Estrogen treatment for prostate cancer is a risk factor for primary breast cancer. Bilateral breast carcinomas were found in a 79-year-old Brazilian black man, following prostate cancer treatment with estrogen. Prostate cancer metastases could be found in breast tissue, and might be indistinguishable from primary breast tumours on histological evaluation without immunohistochemistry. Coexistence of prostate cancer with breast cancer increases future-longevity concerns.
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PMID:Bilateral male breast cancer: too many concerns? 1826 Jul 45

The objective of our study was to investigate the prevalence of prostate disease in general male population. Also, an extended analysis of medical history, behavior and hormonal analysis was performed. 1000 candidates were randomly selected out of voluntary male population. 977 of those were included in the study, and 23 were rejected because of incomplete data, unwillingness to be subjected to examination and other reasons. Blood samples were taken from all participants, and a questionnaire and physical examination (with rectal exam) were performed. Based on the results, answers and the examination all participants were divided in four groups. The prevalence of benign prostate hyperplasia was 23.1%, of prostatitis 5.1% and of prostate cancer 3.7%, which is within expected reported values. Family history data provided little specific data. Significant lower urinary tract symptoms were found in both subjects with benign prostate hyperplasia and prostatitis, showing a strong overlap of symptoms. The results indicate that alcohol abuse is strongly related to subjects with prostate cancer, although this relation is not confirmed by all authors. On the hormonal scale we found higher levels of binned testosterone in our subjects with prostate cancer, what is disproved by some authors. Estrogen is found in higher levels and recent reports are showing higher levels of estrogen metabolites in prostate cancer subjects. Also we found lower levels of vitamin D in subjects with benign prostate hyperplasia and prostate cancer. Since vitamin D is known to inhibit cellular proliferation, lower levels are confirmatory, with its loss of protective role against prostate cancer. Our results suggest that male population in Croatia (at least in Slavonia) with prostate diseases is, with all findings taken into account, within limits as compared to populations in developed European countries, but on a lower border. Since the prevalence of investigated diseases is rising throughout Europe we could expect the same trends in our country.
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PMID:Prostate disease prevalence with epidemiological and hormonal analysis in randomly selected male population in Croatia. 1914 28

Estrogen may be involved in the development of prostate cancer. The association between genetic polymorphisms of estrogen receptors alpha (ESR1) and beta (ESR2) and prostate cancer risk was examined in a nested case-control study in Washington County, Maryland. Incident prostate cancer cases (n = 269) were matched to one or two controls (n = 440) by age, sex, race, and date of blood donation. Associations between estrogen receptor genotypes or dietary intake and the development of prostate cancer were examined in conditional logistic regression models. Results from this study showed that six single base-pair polymorphisms (SNPs) of ESR1 (rs1801132, rs2077647, rs746432, rs2273206, rs851982, rs2228480) and four SNPs of ESR2 (rs4986938, rs928554, rs8018687, rs number not available for ESR2 5696 bp 3' of STP A>G) were not significantly associated with prostate cancer risk, either by allelic or genotypic frequencies. However, an interactive association with BMI was observed in the relationship between prostate cancer risk and genotypes of ESR2 38 bp 3' of STP G>A (rs4986938) (p = 0.031). An interaction between intake level of phytoestrogen and genotypes of ESR1 Ex1-192G>C (rs746432) and between intake level of phytoestrogen and genotypes of ESR1 Ex8+229G>A (rs2228480) and risk of prostate cancer was observed (p = 0.0009 and p = 0.044, respectively). In conclusion, selected genetic polymorphisms of ESR1 and ESR2, overall, were not associated with prostate cancer risk. However, a variation in risk by BMI and phytoestrogen intake was implicated.
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PMID:Genetic polymorphisms of estrogen receptors alpha and beta and the risk of developing prostate cancer. 1965 68

Estrogen is suspected to play a role in the pathogenesis of benign prostatic hyperplasia (BPH) and prostate cancer. To clarify the role of estradiol (E2) in the prostatic tissues (prostatic tissue E2) during the development of prostatic disorders, we developed a new sensitive and specific quantification method for prostatic tissue E2 using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For the solid-phase extraction, E2 was purified by anion-exchange through an Oasis MAX cartridge. In addition, after the formation of 3-pentaflurobenzyl-17beta-pyridinium-estradiol derivative (E2-PFBPY), E2-PFBPY was purified by cation-exchange through an Oasis WCX cartridge. These processes in the LC-MS/MS method improved the specificity and sensitivity for prostatic tissue E2 measurement, compared to the radioimmunoassay (RIA) method. The validation tests showed that intra-day and inter-day precisions were both within +/-15% (except for 15.5% of the inter-day precision of the lowest concentration), with the accuracy ranging from 88 to 110%. The quantification limit of this assay was 0.15pg/tube in our method, which was 80-fold more sensitive than that of the RIA method. With the use of our present method, the median E2 levels in the prostatic tissues in patients with BPH (n=20, median age: 71 years) were 12.0pg/g tissue (95% confidence interval=9.1-22.6pg/g tissue). Furthermore, the E2 levels increased significantly with aging. These results showed that our present method would be useful for elucidating the role of prostatic tissue E2 in the development of prostatic disorders with a small amount of tissue samples.
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PMID:New quantification method for estradiol in the prostatic tissues of benign prostatic hyperplasia using liquid chromatography-tandem mass spectrometry. 1976 67


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