Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Testosterone is converted to dihydrotestosterone by 5 alpha-reductase2 in the prostate. Dihydrotestosterone controls cell division, and interindividual differences in prostatic 5 alpha-reductase 2 expression and activity may be a determinant of the risk of developing prostate cancer. However, little is known about interindividual differences in intraprostatic hormonal activity in vivo. To determine whether 5 alpha-reductase-specific messenger RNA (mRNA) is predictive of 5 alpha-reductase activity in prostatic tissue, we analyzed 30 prostatic tissue specimens from 15 Caucasian patients, 47--82 yr old. The mRNA was measured by RT-PCR. Five specimens consisted of cancer, whereas the remaining 25 were derived from benign prostate hyperplasia (BPH). We found a strong association between enzyme activity at pH 5.5 and the 5 alpha-reductase 2-specific mRNA expression when expressed on the basis of beta-actin [Spearman's rank-correlation coefficient (r(s)) = 0.81; 95% confidence interval, 0.64-0.91; P < 0.0001]. The expression of 5 alpha-reductase 2-specific mRNA in the cancer specimens was significantly lower than in the BPH tissue (P = 0.03). There was no difference in the expression of 5 alpha-reductase 1-specific mRNA in the cancer specimens, compared with BPH (P = 0.56). The strong association between 5 alpha-reductase activity at pH 5.5 and the 5 alpha-reductase 2-specific mRNA expression makes it possible to predict prostatic 5 alpha-reductase activity using core needle biopsies.
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PMID:Messenger ribonucleic acid levels of steroid 5 alpha-reductase 2 in human prostate predict the enzyme activity. 1115 57

The efficacy of combination suicide gene therapy was evaluated using a Herpes simplex virus-thymidine kinase/ganciclovir (HSV-TK/GCV) system and an Escherichia coli cytosine deaminase/5-fluorocytosine (CD/5-FC) system on the LNCaP human prostate cancer cell model. Two types of plasmid vectors with the HSV-TK gene were constructed. A constitutive chicken beta-actin promoter drove one and a prostate-specific antigen (PSA) promoter drove the other. Similarly, a pair of plasmids with the CD gene under a cytomegalovirus (CMV) promoter and the PSA promoter was also constructed. LNCaP cells were transfected in vitro with either or both of those plasmids using a cationic lipid reagent. Transfected cells were treated with GCV and/or 5-FC. The percentage of viable LNCaP cells 7 days after treatment with HSV-TK/GCV or CD/5-FC under a constitutive promoter was 40% and 41% of controls, respectively. The cell viability when two suicide genes were combined was 23%. The cell viabilities after four days with PSA promoter-HSV-TK vectors, CD vectors and a combination of both were 79%, 88% and 88%, respectively. Suicide gene therapy using either HSV-TK/GCV, CD/5-FC, or both, was effective in the LNCaP model. An additive effect was observed when the two suicide genes were used together. The PSA promoter did not seem to be effective enough to elicit cytotoxicity under the experimental conditions used here.
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PMID:Suicide gene therapy on LNCaP human prostate cancer cells. 1144 69

There are few options for treating hormone-refractory prostate cancer (PC). Various studies indicate that luteinizing hormone-releasing hormone (LHRH) agonists may have a direct inhibitory effect on prostate tumors mediated by specific LHRH receptors. One study evaluated LHRH receptors in hormone-dependent PC tissue, but no data have thus far been obtained on the presence of LHRH receptors in benign prostatic hyperplasia (BPH) and especially hormone-refractory PC in patients. Thus, it is not yet clear whether LHRH receptors indicate tumor-related differentiation or even hormone-refractory dedifferentiation or are likewise associated with BPH. The aim of this study was to determine the rate of LHRH receptor mRNA expression in BPH and in primary, potentially androgen-dependent and in hormone-refractory PC with clinical progression. Multiplex reverse transcription-PCR was used to simultaneously detect the expression of mRNA for LHRH receptors and beta-actin in 48 patients with BPH, 14 with a primary, possibly hormone-dependent, prostate carcinoma (PPC), and 18 with a hormone-refractory prostate carcinoma (HRPC). Sixteen of 18 samples with HRPC showed intact RNA and expressed mRNA for LHRH receptors (100%). However, the RNA-intact PPC and BPH showed significantly lower expression of mRNA for LHRH receptors (46.2 and 55.3%, respectively; variance analysis: P = 0.0017). The significantly higher expression of mRNA for LHRH receptors in HRPC indicates that therapeutic concepts should be developed that target this site of action. In addition to possible direct effects of LHRH agonists or antagonists demonstrated previously in vitro, it seems useful to apply targeted cytotoxic LHRH analogues or monoclonal antibodies.
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PMID:Increased incidence of luteinizing hormone-releasing hormone receptor gene messenger RNA expression in hormone-refractory human prostate cancers. 1148 10

Human prolactin (hPRL) has been reported to be involved in breast and prostate cancer development. The hPRL receptor (hPRLR) is expressed in a wide variety of tissues in at least three isoforms. In this study, a one-step real time reverse transcription PCR technique was used to determine relative expression levels of hPRLR mRNA in eleven human breast cancer cell lines, HeLa cells, three prostate cancer cell lines and nine normal human tissues. The housekeeping gene beta-actin was used for internal normalization. We demonstrate that hPRLR mRNA is up-regulated in six of the eleven breast cancer cell lines tested when compared with normal breast tissue. Of the cancer cell lines tested, we found that T-47D cells have the highest level of hPRLR mRNA, followed by MDA-MB-134, BT-483, BT-474, MCF-7 and MDA-MB-453 cells. In two breast cancer cell lines (MDA-MB-468 and BT-549), the hPRLR levels were found to be comparable to that of normal breast tissue. Three breast cancer cell lines (MDA-MB-436, MDA-MB-157 and MDA-MB-231) expressed hPRLR mRNA at levels lower than that of normal tissue. In contrast, in all three commonly used prostate cancer cell lines (LNCaP, PC-3 and DU 145), the levels of hPRLR mRNA were found to be down-regulated relative to that of normal prostate tissue. Of nine normal human tissues tested, we found that the uterus and the breast have the highest levels of hPRLR mRNA, followed by the kidney, the liver, the prostate and the ovary. The levels of hPRLR mRNA were the lowest among the trachea, the brain and the lung.
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PMID:Quantification of prolactin receptor mRNA in multiple human tissues and cancer cell lines by real time RT-PCR. 1157 5

Capillary electrophoresis with laser-induced fluorescence detection was used to monitor gene expression in individual mammalian cells using the reverse transcriptasepolymerase chain reaction. Specifically, beta-actin expression in single LNCaP (prostate cancer) cells was measured. A sieving matrix containing hydroxypropyl methyl cellulose was used to effect size-based separation. Ethidium bromide fluorescence of the product DNA was used as the detection scheme and yielded excellent sensitivity. The beta-actin product, resulting from an individual cell lysed by a freeze-thaw method, gave an average signal-to-noise ratio (S/N) of 77+/-27 (n = 2). Chemical lysis of a single cell, using a dilute solution of SDS, gave a S/N of 26+/-2 (n = 2), roughly 3-fold lower than for freeze-thaw lysis. An initial detection limit (not considering fully optimized conditions) was calculated from an amplified cDNA standard to correspond to a concentration of approximately 133 starting molecules/nL (of beta-actin mRNA).
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PMID:Measurement of single-cell gene expression using capillary electrophoresis. 1177 20

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme best known to many investigators as a 'housekeeping' gene used as a loading control on northern blots. Prior studies, however, have shown that GAPDH RNA levels vary greatly among different prostate cancer cell lines. We undertook this study to determine the level of GAPDH gene expression within primary human prostate tumors and to determine the validity of using GAPDH as a loading control for northern analysis of human prostate cancer specimens and normal human organs. We found that GAPDH expression was significantly higher in specimens from patients with pathological stage C and D prostate cancer than those with stage B disease. Within the human prostate cancer cell lines TSUPr1, DU145, LNCaP and PC-3 and a normal neonatal prostate epithelial cell line FNC 267beta1, LNCaP cells expressed the highest level of GAPDH but all cell lines, including the normal neonate prostate cell line had very strong GAPDH gene expression. GAPDH RNA levels were highly variable among 16 normal human adult organs and four human fetal organs examined. We conclude that GAPDH RNA levels in human prostate tumors correlate with pathologic stage and that GAPDH should not be used as a loading control in northern blot experiments. Other controls, such as beta-actin or 28s ribosomal RNA, would be more suitable for such purposes.
Prostate Cancer Prostatic Dis 1997 Dec
PMID:Increased glyceraldehyde-3-phosphate dehydrogenase gene expression in late pathological stage human prostate cancer. 1249 18

Oxidative damage is an important factor in prostate carcinogenesis, and overexpression of human MutT homolog (hMTH), a repair gene that removes oxidative damage, is a molecular marker of cellular oxidative stress. Therefore, we tested the hypothesis that overexpression of hMTH in unaffected (normal) surrogate tissue is associated with risk of prostate cancer in a pilot study of 51 patients with diagnosed prostate cancer and 50 age- and ethnicity-matched controls. Total RNA was extracted from phytohemagglutinin-stimulated peripheral blood lymphocytes of these subjects. We performed the real-time reverse transcription-polymerase chain reaction assay to evaluate the relative mRNA expression of three oxidative-damage-repair genes, human MutM homolog (hMMH), hMTH, and human MutY homolog (hMYH), with beta-actin and human O(6)-methylguanine DNA methyltransferase (hMGMT) as the internal controls. The relative gene expression levels of hMMH and hMTH were borderline higher in the cases than in controls (15.3% and 28.8% higher, respectively; P = 0.046 and P = 0.035, respectively), whereas no increase was observed for hMYH and hMGMT. With the median of the controls' values as the cutoff point, we observed that a high expression level of hMTH, but not of other genes, was associated with a significantly increased risk of prostate cancer (odds ratio = 2.62; 95% confidence interval = 1.13-6.75) after adjustment for age and ethnicity. These results suggested that increased expression of hMTH in peripheral lymphocytes may be a risk factor for prostate cancer and support our priori hypothesis. Although our findings were biologically plausible and consistent with the literature, they were preliminary and need to be confirmed in larger studies. In addition, a correlation between the expression level of hMTH and the level of oxidative DNA damage in the target tissues needs to be established as well.
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PMID:Overexpression of hMTH in peripheral lymphocytes and risk of prostate cancer: a case-control analysis. 1261 34

Nitric oxide (NO) is an important signaling molecule for ischemia, inflammation, angiogenesis, immune response, and cell growth and differentiation. It has recently been shown that increased production of NO within various human cancers may contribute to tumor angiogenesis, tumor growth and metastasis, and tumor-related immune suppression. NO can be produced by several NO synthases (NOS), including inducible synthase (iNOS), which is expressed during cell activation and produces NO in larger quantity and for a longer period of time than non-inducible NOSs. In this study, we examined the expression levels of iNOS mRNA and protein in prostate adenocarcinoma using a paired nonneoplastic and neoplastic primary prostate cell culture system and related prostatectomy specimens. Six pairs of neoplastic and nonneoplastic primary prostate cell cultures were established from radical prostatectomy specimens based on homogeneity of the originating tumor and the nonneoplastic tissue. Radioactive reverse transcriptase polymerase chain reaction and subsequent quantitative analysis of iNOS mRNA were performed on the cultures using beta-actin as an internal control. Immunohistochemical studies with an anti-iNOS monoclonal antibody were performed on the corresponding formalin-fixed paraffin-embedded prostatectomy tissue sections. We observed marked patient-to-patient variation in "normal" levels of iNOS mRNA. However, all six neoplastic cultures showed moderately to markedly higher mRNA levels than did their paired nonneoplastic cultures. In addition, iNOS protein levels were significantly higher in paraffin-embedded prostate cancer tissue sections than in adjacent nonneoplastic tissue. Overexpression of iNOS mRNA and protein levels is present in moderately differentiated prostate adenocarcinoma and may contribute to prostate cancer angiogenesis, tumor growth, and tumor-related immunosuppression.
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PMID:Expression of inducible nitric oxide synthase in paired neoplastic and non-neoplastic primary prostate cell cultures and prostatectomy specimen. 1285 39

Prostate cancer is one of the most common cancers among men. Recent studies demonstrated that PI3K signaling is an important intracellular mediator which is involved in multiple cellular functions including proliferation, differentiation, anti-apoptosis, tumorigenesis, and angiogenesis. In the present study, we demonstrate that the inhibition of PI3K activity by LY294002, inhibited prostate cancer cell proliferation and induced the G(1) cell cycle arrest. This effect was accompanied by the decreased expression of G(1)-associated proteins including cyclin D1, CDK4, and Rb phosphorylation at Ser780, Ser795, and Ser807/811, whereas expression of CDK6 and beta-actin was not affected by LY294002. The expression of cyclin kinase inhibitor, p21(CIP1/WAF1), was induced by LY294002, while levels of p16(INK4) were decreased in the same experiment. The inhibition of PI3K activity also inhibited the phosphorylation and p70(S6K), but not MAPK. PI3K regulates cell cycle through AKT, mTOR to p70(S6K). The mTOR inhibitor rapamycin has similar inhibitory effects on G(1) cell cycle progression and expression of cyclin D1, CDK4, and Rb phosphorylation. These results suggest that PI3K mediates G(1) cell cycle progression and cyclin expression through the activation of AKT/mTOR/p70(S6K) signaling pathway in the prostate cancer cells.
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PMID:Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. 1455 32

We report here the development of the transgenic green fluorescent protein (GFP) nude mouse with ubiquitous GFP expression. The GFP nude mouse was obtained by crossing nontransgenic nude mice with the transgenic C57/B6 mouse in which the beta-actin promoter drives GFP expression in essentially all tissues. In crosses between nu/nu GFP male mice and nu/+ GFP female mice, the embryos fluoresced green. Approximately 50% of the offspring of these mice were GFP nude mice. Newborn mice and adult mice fluoresced very bright green and could be detected with a simple blue-light-emitting diode flashlight with a central peak of 470 nm and a bypass emission filter. In the adult mice, the organs all brightly expressed GFP, including the heart, lungs, spleen, pancreas, esophagus, stomach, and duodenum. The following systems were dissected out and shown to have brilliant GFP fluorescence: the entire digestive system from tongue to anus; the male and female reproductive systems; brain and spinal cord; and the circulatory system, including the heart and major arteries and veins. The skinned skeleton highly expressed GFP. Pancreatic islets showed GFP fluorescence. The spleen cells were also GFP positive. Red fluorescent protein (RFP)-expressing human cancer cell lines, including PC-3-RFP prostate cancer, HCT-116-RFP colon cancer, MDA-MB-435-RFP breast cancer, and HT1080-RFP fibrosarcoma were transplanted to the transgenic GFP nude mice. All of these human tumors grew extensively in the transgenic GFP nude mouse. Dual-color fluorescence imaging enabled visualization of human tumor-host interaction by whole-body imaging and at the cellular level in fresh and frozen tissues. The GFP mouse model should greatly expand our knowledge of human tumor-host interaction.
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PMID:Transgenic nude mouse with ubiquitous green fluorescent protein expression as a host for human tumors. 1557 73


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