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

The effects of androgen and epidermal growth factor (EGF) on cell proliferation and the expression of mRNA and protein of androgen receptor (AR) were examined in an androgen-sensitive human prostatic cancer cell line, LNCaP, by Northern and Western blot analyses. The addition of 1 nM dihydrotestosterone (DHT), at which the proliferation of the cells was most stimulated, did not change the level of AR mRNA but increased the level of AR protein by reducing the turnover rate of the AR protein. EGF also stimulated the proliferation of the cells but repressed the expression of AR mRNA and protein. This repression was found to be exerted primarily at the level of transcription. When DHT and EGF were added simultaneously to the cells, the level of AR mRNA was reduced to the same degree as was accomplished by the addition of EGF alone. On the other hand, the level of AR protein increased but this increase was about 70% of that attained following the addition of DHT alone. The stimulatory effects of EGF and DHT on cell proliferation were found to be additive. These results indicate that EGF down-regulates the level of AR mRNA and thereby also that of AR protein irrespective of the presence of DHT, and that EGF stimulates the proliferation of LNCaP cells through a different pathway from that of DHT.
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PMID:Regulation of androgen receptor by androgen and epidermal growth factor in a human prostatic cancer cell line, LNCaP. 142 49

Previously, we established an anti-androgen receptor (AR) monoclonal antibody. Using the antibody, we investigated immunohistological AR localization in human testes, epididymides, seminal vesicles and scrotal skins. The testes, epididymides and scrotal skins were obtained from a prostate cancer patient without pre-hormonal therapy undergoing bilateral orchiectomy. The seminal vesicles were obtained from a bladder cancer patient undergoing radical cystectomy. The tissues were immediately frozen in liquid nitrogen and kept at -80 degrees C until used. Cryostat-frozen sections were cut at 5 microns and stained by an indirect method. We obtained the following results. 1) In the testes, nuclei of Leydig cells were stained though Sertoli cells were not stained. AR localization in Leydig cells which produce testosterone suggests autocrine or intracrine mechanism in the testis. 2) In the epididymides, nuclei of epithelial cells of epididymal ducts were stained, while muscles and connective tissues were not stained. In the seminal vesicles, nuclei of glandular epithelial cells were stained. 3) In the scrotal skins, the cells of squamous cell layer have positive stainings. The cells in the upper portion of squamous cell layer were stained more intensely than the cells in the lower portion. The basal layer was not stained. The cells of the outer root sheath of hair follicles in the scrotal skins were also stained. 4) In androgen target organs, AR-positive cells and AR-negative cells were mixed in the epithelium of a glandular duct, which suggests heterogeneity of AR localization in the androgen target organs.
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PMID:[Localization of androgen receptor in male sex organ, accessory sex organs and external genital skin]. 147 18

This article reviews the present understanding of chromosomal aberrations and specific genetic mutations in renal, bladder, and prostate cancers. In kidney tumors, specific emphasis is given to chromosome 3 deletions in renal cell carcinoma and the characterization of the WT1 gene in Wilms' tumor. In all three urological tumors, the presence of mutations in the RAS, P53, and RB genes (all of which often occur in other tumors) is analyzed. The expression and properties of the androgen receptor in prostate cancer are also summarized.
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PMID:The molecular biology of urological tumors. 157 58

We have prepared nine androgens substituted with fluorine at C-16 or C-20 to evaluate their potential, as positron emission tomographic (PET) imaging agents for prostatic cancer when labeled with the positron emitting radionuclide fluorine-18 (t1/2 = 110 min). These compounds represent members from the following classes of androgens: testosterone (T), 5 alpha-dihydrotestosterone (DHT), 7 alpha-methyl-19-nortestosterone (MNT), mibolerone (Mib), and metribolone (R1881). All of these compounds were prepared by functionalization of suitable androgen precursors, and the synthetic routes were developed to allow the introduction of fluorine by a fluoride ion displacement reaction late in the synthesis, as is required for the preparation of these compounds in fluorine-18 labeled form. We have also prepared four androgens in which the C-3 carbonyl or 17 beta-hydroxyl groups are replaced by fluorine. Most of the fluorine-substituted androgens show high affinity for the androgen receptor (AR), although fluorine substitution lowers their affinity by a small factor. None of the androgens where fluorine replaces oxygen functions at C-3 or C-17 have substantial affinity for AR. Derivatives of the natural androgens (T and DHT) as well as MNT have little affinity for other steroid hormone receptors (progesterone and mineralocorticoid receptors), whereas the Mib and R1881 derivatives have somewhat greater heterologous binding. With sex steroid binding protein, a human serum binding protein, the pattern of binding affinities is nearly the reverse, with derivatives of Mib, R1881 and MNT having low affinity, and DHT and T, high affinity. From these fluorine-substituted compounds, we can select several whose preparation in fluorine-18 labeled form for further tissue distribution studies is merited.
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PMID:Synthesis of high affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomography. 159 61

The metastatic capacity of PA-III rat prostate adenocarcinoma cells has been well documented, although little is known about the biological and biochemical characteristics of PA-III cells. This study characterizes PA-III cells with regard to the presence or absence of glucocorticoid and androgen receptors. Cytosols of PA-III cells possessed [3H]-dexamethasone binding sites with association constant (Ka) 0.46 +/- 0.17 x 10(9) M-1 and number 341 +/- 175 fmols/mg protein. Displacement of [3H]-dexamethasone binding from PA-III cytosols achieved by increasing doses of unlabelled dexamethasone, corticosterone, cortisol, progesterone, deoxycorticosterone and aldosterone documented glucocorticoid binding specificity. Northern and dot blot analyses detected the expression of mRNA for glucocorticoid receptor using a 750 bp cDNA probe of the glucocorticoid receptor gene. Twenty-four hours incubation of PA-III cells with increasing amounts of dexamethasone resulted in a remarkable inhibition of the growth of PA-III cells. Binding studies with [3H]-R1881 as well as dot blot and Northern blot analyses using a 500 bp cDNA probe of androgen receptor gene could not detect the presence of androgen receptors in PA-III cells. The present study documented functional glucocorticoid receptors in the androgen-independent PA-III rat prostate adenocarcinoma cells. These results suggest that glucocorticoids may regulate important aspects of androgen-independent prostate cancer cells growth and functions.
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PMID:The expression of mRNA for glucocorticoid receptor gene and functional glucocorticoid receptors detected in PA-III rat prostate adenocarcinoma cells. 162 47

We screened human prostate cancer tissues for the presence of somatic mutations in the hormone binding domain of the androgen receptor (AR) gene. Exons E-H were amplified from genomic DNA using the polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE), which separates DNA fragments that differ by only a single base. We detected a mutation in exon E of the hormone binding domain in 1 of 26 specimens of untreated organ-confined stage B prostate cancer. The mutation was not detectable in peripheral blood lymphocyte DNA. Lymphocyte DNA (wild-type AR) migrated in DGGE as a single band. The tumor DNA migrated in DGGE as four bands, consistent with the presence of cells with mutant AR plus cells with wild-type AR and indicating that the tumor contained a somatic mutation. To our knowledge, a somatic AR gene mutation has not been reported previously. Sequencing revealed a G----A substitution in codon 730, changing valine to methionine. Codon 730 is in a region highly conserved among all steroid receptors. The abundance of the mutated fragment (about 50% of the DNA in the specimen) indicates its presence in cells with a growth advantage. A somatic mutation could be detected by DGGE if it represented at least 10% of the sample. Failure to detect mutations in other specimens analyzed may be due to this limit of sensitivity, the presence of mutations in other parts of the AR, or a low frequency of mutations in early stage disease.
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PMID:Androgen receptor gene mutations in human prostate cancer. 163 Nov 25

The gene for the androgen receptor (AR) in the androgen-sensitive human prostate cancer cell line LNCaP has a single-base mutation that produces a threonine to alanine change in the androgen-binding domain. Androgen-insensitive prostatic cancer (PC-3) cells were cotransfected with an expression vector encoding normal, LNCaP, or chimeric normal/LNCaP AR and a vector carrying a chloramphenicol acetyltransferase (CAT) reporter gene linked to the mouse mammary tumor virus promoter. CAT activity was specifically induced by androgens in PC-3 cells expressing normal AR. In PC-3 cells expressing LNCaP AR, however, CAT activity was also induced by progestins and the antiandrogen hydroxyflutamide, which had little activity in cells expressing normal AR. Steroid-binding competition assays using in vitro synthesized ARs showed that LNCaP AR had a higher affinity than normal AR for progestins, 17 beta-estradiol, and hydroxyflutamide. The antiprogestin and antiglucocorticoid RU 38486 induced CAT activity in PC-3 cells expressing normal AR but not LNCaP AR. These studies indicate that AR mutations may be very important in determining the appropriate method of treatment with steroid hormones or their antagonists.
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PMID:Expression and function of normal and LNCaP androgen receptors in androgen-insensitive human prostatic cancer cells. Altered hormone and antihormone specificity in gene transactivation. 166 32

A longstanding goal has been to determine whether androgen receptor (AR) levels could be used to predict the clinical response of metastatic prostate cancer to androgen withdrawal therapy. A major limitation of previous studies was the use of homogenized tissue, which yields an average AR content for all cells. By AR immunohistochemical study using an antibody specific for AR the authors assessed nuclear AR content specifically in the malignant epithelial cells of prostate needle biopsy specimens of 17 patients with Stage D prostate cancer. The authors found that prostate cancer contains AR-positive and AR-negative malignant cells before androgen withdrawal therapy, but the percentage of AR-positive cells did not predict the time to tumor progression after therapy. There was no significant correlation between the percentage of AR-positive malignant cells and the time to tumor progression. When patients were divided into two groups based on the median time to progression, the percentage of AR-positive nuclei was not significantly different in poor responders versus good responders. When patients were divided into two groups based on the median percentage of receptor-positive nuclei, Kaplan-Meier estimates of the progression-free interval revealed no significant difference between the group of patients with AR-poor tumors and patients with AR-rich tumors. Potential explanations for these results are discussed. The authors conclude that the percentage of AR-positive nuclei is not a sufficient criterion to predict tumor behavior.
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PMID:Immunohistochemical study of androgen receptors in metastatic prostate cancer. Comparison of receptor content and response to hormonal therapy. 171 May 37

Experiments have been designed to investigate hormonal effects on the human prostatic carcinoma cell line LNCaP in the presence of complete foetal calf serum. At physiological concentrations (3.3 x 10(-9)M), several derivatives of 17 alpha-methyl-testosterone led to a significant reduction of cell proliferation, inhibition of colony formation in soft agar, change of morphology, induction of a prostate specific mRNA and down-regulation of c-myc RNA. Two different antiandrogens, hydroxyflutamide and cyproterone acetate, were capable of reversing the effects exerted by the synthetic androgens on growth properties. The proliferation rate of control cells devoid of androgen receptor was not inhibited by synthetic androgens. Our results indicate that the cellular androgen response mechanism of LNCaP cells is intact and that synthetic androgens elicit androgen receptor mediated suppression of the transformed phenotype. Rare cases of remission of prostatic cancer on androgen treatment have been reported. LNCaP cells may be a model of an uncommon class of prostatic cancer which responds favourably to androgen treatment.
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PMID:Synthetic androgens suppress the transformed phenotype in the human prostate carcinoma cell line LNCaP. 171 53

Prostate cancer is the most frequent cancer in men. A discovery of major importance in the endocrinology of prostate cancer is that the testes contribute only 60% of total androgens in adult men; the remaining 40% are synthesized in peripheral tissues, including the normal and cancerous prostate, from inactive androgen precursors of adrenal origin. Using a combination therapy that includes a pure blocker of the androgen receptor or antiandrogen and castration (medical with luteinizing hormone-releasing hormone agonist or surgical by orchiectomy), the duration of response and survival have been demonstrated to be prolonged for the first time in advanced prostate cancer.
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PMID:Endocrine therapy for prostate cancer. 177 80


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