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)

The use of multiple tumor markers could better predict the behavior of malignant tumors. In prostate cancer, there are no reliably predictive markers for metastatic behavior but the histologic grade and clinical stage of tumor do influence prognosis. We have determined the expression of blood group antigens A, B, H, Lewis-a and Lewis-b and the proto-oncogene proteins v-erbB, c-fos and v-H-ras in both benign and malignant prostate tissues by immunohistochemistry. We determined the relationship between these markers and the grade of malignancy and by inference, clinical behavior. There was reduced expression of blood group antigens A, Lewis-a and Lewis-b in all grades of prostatic adenocarcinoma. We also found that the expression of v-erbB was greater in tumors of high grade. We suggest that loss of blood group antigens may be correlated with elevated v-erbB oncoprotein expression (related to epidermal growth factor receptor) and increasing grade of prostatic malignancy.
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PMID:Correlation of blood group antigen expression and oncogene-related proteins in malignant prostatic tissues. 171 71

Specimens of benign prostatic hypertrophy (BPH) and prostate carcinoma and prostate cells in culture were assessed for their capacity to bind androgens, radioiodinated EGF, and IGF-I, and to express certain cellular protooncogenes. Prostate cell lines contained receptors for both EGF and IGF-I. Similarly, clinical samples of human diseased prostate contained receptors for both of these factors. Prostate carcinoma contained higher concentrations of EGF receptors based on DNA than did BPH, although it is accepted that BPH may not be the appropriate comparison for carcinoma. Increased EGF receptors were associated circumstantially with a decline in androgen receptors with deteriorating differentiation status and with an increase in expression of c-myc. Androgen receptor concentration correlated with increased expression of c-fos. Deteriorating differentiation status was associated with the appearance or increase in secondary sites with lower affinity for IGF-I. Whereas c-myc expression was increased in all grades of carcinoma compared to BPH, expression of c-H-ras accompanied loss of differentiation. Although those alterations are hindered by tissue heterogeneity and correlations are essentially circumstantial, they may provide clues to the progression of prostate cancer that can be validated in prostate cell lines with similar growth response capabilities.
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PMID:Growth factor receptors and oncogene expression in prostate cells. 246 69

The role of cellular oncogenes in the development of human prostate cancer has not been extensively studied. A search for activated oncogenes was undertaken by testing DNA isolated from prostatic adenocarcinoma tissues for transforming activity in a 3T3 transfection assay. A transforming sequence homologous to Ki-ras was detected in one of the samples. DNA from the other cancers was negative in the transformation assay, suggesting that the activation of oncogenes, at least those detectable by the 3T3 transfection assay, is not a frequent event in prostate cancer. Amplification of genomic oncogene sequences in prostatic tissues was also examined, but amplification of Ki-ras, Ha-ras, c-myc, N-myc, c-sis, or c-fos was not detectable in any of the samples.
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PMID:Activated Ki-ras oncogene in human prostatic adenocarcinoma. 360 7

The discrepancy between the incidence of latent prostate cancer and that of clinically overt carcinoma suggests that there can be different courses in the biological progression of prostate cancer. As this cancer is detected increasingly at an infraclinical stage, markers are needed to indicate which lesions will progress and lead to the patient's death. To investigate the possibility that specific growth factors and/or proto-oncogenes are expressed differentially, we measured mRNA levels of transforming growth factors beta 1 (TGF-beta 1), TGF-beta 2 and TGF-beta 3 and of the c-fos and c-jun oncogenes by Northern blotting in normal prostate, benign prostatic hyperplasia (BPH) and prostate cancer. Our data demonstrate that expression of TGF-beta 1 increased, whereas that of TGF-beta 3 fell to an almost undetectable level in carcinoma. Expression of c-fos followed the TGF-beta 1 pattern, whereas no difference could be seen in c-jun expression in cancer as compared with BPH and normal prostate. The differential expression of TGF-beta 1, TGF-beta 3 and c-fos could possibly be used to improve the characterisation of prostate cancer. Long-term follow-up of patients may indicate whether mRNA levels of these growth factors and oncogenes correlate clinically and whether they can be used as markers for progression in human prostate cancer.
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PMID:Differential expression of transforming growth factor-beta 1 and beta 3 as well as c-fos mRNA in normal human prostate, benign prostatic hyperplasia and prostatic cancer. 752 82

12-O-tetradecanoyl phorbol ester (TPA) has profound cytotoxic effects on a human prostate cancer cell line, LNCaP. The TPA effect may be mediated via a protein kinase C (PKC) pathway, since staurosporine, a potent PKC inhibitor, could reverse the cell-killing effect. Our studies, based on cellular fragmentation, chromatin condensation, and nuclear fragmentation, suggest that the cell-killing effect is due to apoptosis. Moreover, we also examined expression of early growth response genes and androgen-induced genes in association with TPA-induced apoptosis. Northern blot analysis demonstrated that androgen induction of human glandular kallikrein-1 (hKLK2) mRNA was repressed by TPA in a concentration-dependent manner. A time course study showed that both hKLK2 and c-myc mRNAs were repressed by TPA as early as four hours. In contrast, the steady state mRNA levels for c-fos, c-jun, nerve growth factor induced gene A, and the orphan steroid receptor nur77 were rapidly induced within the first two hours of the treatment. Furthermore, transient co-transfection experiments demonstrated that c-fos and c-jun could repress androgen receptor-mediated gene induction. The above studies suggest that (1) the repression of androgen induction of gene expression by TPA-activated PKC is at least in part due to overexpression of c-jun and c-fos and (2) PKC may be a negative growth regulator in prostate cells.
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PMID:Tumor-promoting phorbol ester-induced cell death and gene expression in a human prostate adenocarcinoma cell line. 784 43

In exploring the biological basis of androgen-independent prostate cancer, we observed serum-independent growth of androgen-independent cells. We then discovered that in androgen-independent but not androgen-dependent cells, the serum-responsive gene c-fos is insensitive to phorbol esters, which regulate c-fos through the same mechanisms as serum. Transient expression of protein kinase C, through which phorbol esters activate c-fos, was sufficient to desensitize c-fos in androgen-dependent cells. Incubation in protein kinase C inhibitor chelerythrine killed androgen-independent but not androgen-dependent cells. This finding implicates protein kinase C activity in androgen-independent prostate cancer and suggests novel therapeutic strategies.
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PMID:c-fos promoter insensitivity to phorbol ester and possible role of protein kinase C in androgen-independent cancer cells. 795 49

Previous studies have demonstrated that androgen responsive human prostate cancer cells can be induced to undergo programmed cell death after androgen ablation. By contrast, androgen-independent human prostate cancer cells do not activate this apoptotic pathway in response to androgen ablation. In the present study, two androgen-independent human prostatic cell lines, PC-3 and DU-145, were used as in vitro model systems to investigate the possibility of induction of programmed cell death in response to non-androgen ablative cytotoxic drugs. Treatment of these cells with the fluorinated pyrimidines, 5-fluoro-2-deoxyuridine or trifluorothymidine, resulted in a significant decrease in cell viability, over a period of 96 hr of exposure to the drugs, as determined by the trypan blue exclusion assay. The characteristic DNA fragmentation into a nucleosomal ladder and induction of expression of specific apoptosis-related genes, such as TRPM-2/SGP-2, and TGF-beta 1, but not the growth-related genes, c-myc, c-fos, and p53, temporally correlated with activation of apoptotic cell death in both systems. Simultaneous treatment with exogenous thymidine completely abrogated the fluoropyrimidine-induced cytotoxic effect in both cell lines, as well as the nucleosomal fragmentation of DNA, indicating that this apoptotic process is due to the induction of "thymineless" state. These results suggest that androgen-independent human prostate cancer cells retain the ability to activate the apoptotic cascade, after treatment with cytotoxic drugs that induce a "thymineless" state.
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PMID:Induction of apoptosis in androgen-independent human prostate cancer cells undergoing thymineless death. 803 80

The intake, as well as serum and urinary concentrations, of phytoestrogens is high in countries where incidence of prostate cancer is low, suggesting a chemopreventive role for phytoestrogens. Their significance could be explained by the ability to antagonize the action of more potent endogenous estrogens in initiation or promotion of tumor formation. We have studied estrogenicity and antiestrogenicity of dietary soy and two phytoestrogens, coumestrol and daidzein, in our neoDES mouse model for the study or prostatic neoplasia. Soy was chosen because it is rich in phytoestrogens, is widely used in Oriental diets, and has antiestrogenic and anticarcinogenic properties in the neoDES mouse when given from fertilization onward. In short-term tests with adult animals, no evidence for estrogenicity or antiestrogenicity (capability to antagonize the action of 17 beta-estradiol) of soy was found when development of epithelial metaplasia and expression of c-fos protooncogene in prostate were used as end points of estrogen action. Estrogenic activity of coumestrol and daidzein on c-fos expression was subtle. Coumestrol, either given alone or in combination with 17 beta-estradiol, had no effect on development of epithelial metaplasia. These marginal or missing effects in adult males could be interpreted by assuming that the neonatal period is more critical for estrogenic or antiestrogenic action of soy and phytoestrogens. Once initiated, estrogen-related lesions would develop spontaneously. Alternatively, the chemopreventive action of soy is not due to antiestrogenicity of soy-derived phytoestrogens.
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PMID:Phytoestrogens are partial estrogen agonists in the adult male mouse. 859 57

LH-releasing hormone (LHRH) agonists exert a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present studies were aimed at clarifying whether these compounds might exert their antiproliferative action by interfering with the stimulatory action of epidermal growth factor (EGF). To this purpose, the effects of a LHRH agonist (Zoladex, LHRH-A) on the mitogenic action of EGF, on some of the EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of the 170-kDa EGF receptor, and c-fos protooncogene expression), as well as on the concentration of EGF receptors have been evaluated. These studies have been performed in both LNCaP and DU 145 cells. The results obtained show that in LNCaP cells, LHRH-A counteracts the mitogenic action of EGF, completely abrogates EGF-induced c-fos expression, and significantly reduces the concentration of EGF-binding sites. The EGF-activated tyrosine phosphorylation of the EGF receptor is not affected by LHRH-A in LNCaP cells. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits the tyrosine phosphorylation of the EGF receptor induced by EGF, and significantly reduces the number of EGF-binding sites. In these cells, LHRH-A is not able to modify the increased expression of c-fos that follows the treatment with EGF. These data suggest that LHRH agonists may inhibit the proliferation of human prostatic tumor cells by interfering with the stimulatory actions of EGF. The intracellular mechanism of action of these compounds appears to differ in androgen-dependent LNCaP and androgen-independent DU 145 cells.
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PMID:Luteinizing hormone-releasing hormone agonists interfere with the stimulatory actions of epidermal growth factor in human prostatic cancer cell lines, LNCaP and DU 145. 892 40

Previous studies have demonstrated that overexpression of urinary plasminogen activator (uPA) in rat prostate cancer cells results in increased skeletal metastases, which are primarily of the osteoblastic variety. The osseous activation induced by the metastases appears to be mediated through the amino terminal fragment (ATF) of uPA, which lacks the catalytic domain and can act as a growth factor for osteoblasts. To explore further the mechanism of action of uPA in bone cells, we evaluated the effects of ATF on modulating the expression of various proto-oncogenes. Human-osteoblast-derived osteosarcoma cells, SaOS2, were treated with graded doses of ATF for 10-120 min, and effects on early response proto-oncogenes were monitored. ATF increased c-myc, c-jun, and c-fos gene expression in a time-dependent manner for up to 60 min, after which mRNA levels fell. The maximum induction was seen in c-fos gene expression, which was found to be dose dependent. This effect of ATF was localized to its growth-factorlike domain. Examination of the half life of these transcripts in the presence of the transcriptional inhibitor actinomycin D demonstrated that ATF does not alter the stability of c-fos mRNA in these bone cells. Nuclear run-off assays indicated that ATF effects were due to stimulation of c-fos gene transcription. An increase in c-fos protein levels was correlated with the augmentation of its mRNA in ATF-treated SaOS2 cells. Pretreatment of SaOS2 cells with the protein tyrosine kinase inhibitor herbimycin and recombinant soluble uPA receptor (uPAR) caused a significant reduction in the ability of ATF to induce c-fos expression. These results demonstrate a novel role for uPA in activating early response proto-oncogenes, in particular c-fos, which plays an important role in bone cell growth and differentiation and may be a key factor in the signal transduction pathway of ATF.
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PMID:Induction in human osteoblastic cells (SaOS2) of the early response genes fos, jun, and myc by the amino terminal fragment (ATF) of urokinase. 925 35


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