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)

Using the mouse prostate reconstitution (MPR) model system, under conditions where the ras and myc oncogenes are introduced via a recombinant retrovirus into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer is produced with high frequency (> 90%) using inbred C57BL/6 mice. Northern blotting and immunohistochemical analysis showed that the transition from benign prostatic hyperplasia (BPH) to prostate cancer is invariably associated with the induction of elevated transforming growth factor-beta 1 (TGF-beta 1) expression. Similar analysis of TGF-beta 1 in human BPH and prostate cancer is consistent with our MPR results and indicates that the accumulation of extracellular TGF-beta 1 is significantly more intense in prostate cancer compared to normal or benign prostate tissues. Interestingly, where benign pathologies are observed in the prostatic stroma in the presence of benign prostatic epithelium, extracellular TGF-beta 1 is seen predominantly in the stromal compartment. Experimental studies clearly demonstrate that mRNA levels of TGF-beta 1 and other growth related genes are regulated by androgens in prostate cancer cells. Overall, our results suggest that elevated TGF-beta 1 is involved in the development of prostate cancer. Direct determination of TGF-beta 1 levels and distribution as well as analysis of localized and systemic effects produced by TGF-beta 1 may serve as useful biomarkers for prostate cancer.
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PMID:Transforming growth factor beta 1 as a biomarker for prostate cancer. 128 74

We review in this paper the role of heparin-binding growth factor (HBGF*) or fibroblast growth factor (FGF*), rat prostate cancer cells produce TGF-beta, IGF-II* and OGF*. Of these growth factors, TGF-beta and unknown labile factor with 19 kDa are the most probable candidates responsible for osteoblastic bony metastasis of prostate cancer. In vitro experiments suggest that TGF-beta modulates cell detachment of prostate cancer cells together with nutritional factors. HBGF-dependent growth of the prostate tumor epithelial cells is free from inhibition by TGF-beta, whereas normal prostate epithelial cells are sensitive to TGF-beta inhibition. Transfection experiments suggest that HBGF-2 (basic FGF) might be closely related to the malignant growth of prostate cancer, in addition to tumor angiogenesis.
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PMID:Potential role of HBGF (FGF) and TGF-beta on prostate growth. 149 11

Normal and abnormal developmental events in the prostate are strongly influenced by androgens. There is abundant evidence, however, that androgens are not the only substances present that have the capacity to influence prostatic growth. A number of polypeptides that either stimulate or inhibit growth have now been identified in the prostate. These include members of the HBGF family, TGF-beta family, EGF and TGF-alpha, PDGF, NGF, and the less well characterized osteoblast growth factors. In some cases, the prostatic cell population, stromal or epithelial, that synthesizes the growth factor and its receptor is known. This information and the properties of the growth factors suggest ways in which these polypeptides may be involved in regulating growth of the prostate, including benign prostatic hyperplasia and prostate cancer.
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PMID:Polypeptide modulators of prostatic growth and development. 172 87

The mouse prostate reconstitution model exploits the ability of the fetal urogenital sinus to differentiate into a mature prostate when grafted under the renal capsule of an adult isogenic male host. By use of a recombinant retroviral vector, the ras and myc oncogenes are introduced singly or in combination into the fetal urogenital sinus--resulting in distinct phenotypes of prostatic pathology: dysplasia (caused by ras), hyperplasia (caused by myc) and frank carcinomas (caused by a combination of ras+myc). This unique experimental model creates in vivo conditions that mimic the natural initiation and progression of cancer. An expanded MPR protocol allows restricted retrovirus infection of the mesenchyme or epithelial compartments to evaluate paracrine activities. It enables almost unparalleled flexibility in addressing fundamental questions in prostate cancer. We have identified genetic variance in the susceptibility to tumour induction between two different strains of mice (mimicking the observation of racial variability in the predisposition to clinical prostate cancer). The MPR model supports data from other tumour models and implicates TGF-beta 1 and TGF-beta 3 as being strongly associated with tumour progression. Finally, with this model, we have established clonal prostate adenocarcinomas to study directly the affects of castration on gene expression. Not only are TGF-beta 1 and TGF-beta 3 mRNA levels increased in association with malignancy but they are also further enhanced by castration treatment. Based on these experimental studies, we believe that TGF-beta 1 and TGF-beta 3 expression strongly influences the progression of prostate cancer. This information will hopefully impact on the development of more effective therapy for this important malignancy.
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PMID:Experimental oncogene induced prostate cancer. 172 89

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

Advanced prostatic cancer (PC) involves a serious prognosis. PC cells form growth factors, which affect growth in autocrine or paracrine manner. PC cell lines, hormone dependency, and growth modalities are mentioned. Interference with these model systems by TGF-alpha, TGF-beta and EGF is described. The presence of less characterized growth factors in homogenates and conditioned media from PC cells is mentioned. An abundance of EGF and EGF-receptors has been found in PC compared to BPH samples. New strategies for treatment are outlined.
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PMID:[Prostatic cancer and growth factors]. 223 65

A colony formation assay using NRK-49F cells revealed that a metastatic cell line, AT-3, established from the Dunning prostatic carcinoma could produce TGF-beta in a latent form. TGF-beta at a concentration as low as 0.05 ng/ml either stimulated the attachment or detachment of AT-3 cells depending on the kind of culture media. Acid extracts from conditioned medium (5 micrograms/ml) showed the activity comparable to that of TGF-beta (5 ng/ml). The detached cells were able to grow in suspension. TGF-beta (0.1 ng/ml) could also stimulate the growth of MC3T3-El osteoblasts established from mouse calvaria. These results suggest that TGF-beta is a key growth factor for osteoblastic bony metastasis of prostate cancer.
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PMID:Production and significance of TGF-beta in AT-3 metastatic cell line established from the Dunning rat prostatic adenocarcinoma. 230 41

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

Prostate-specific antigen (PSA), a M(r) 34,000 serine protease, is recognized as a useful marker for the detection and prognosis of patients with prostate cancer. Although serum PSA is an excellent prognostic indicator, an increasing number of factors were found to regulate the PSA expression of prostatic cancer cells, which include androgenic steroids, the growth factors (GFs) and the extracellular matrix. The purpose of this study is to define a novel protein factor that may be responsible for regulating PSA expression by androgen-independent (AI) human prostate cancer cells. We have established a LNCaP subline (C4) from a parental LNCaP tumor grown in a castrated host. The C4 subline overexpressed PSA mRNA and protein. Serum-free conditioned medium (CM) isolated from the C4 subline is able to stimulate PSA gene expression in parental LNCaP cells in a concentration-dependent manner. This autocrine PSA-inducing activity was found to be organ specific because CMs from other fibroblast cell lines (such as bone, prostate, kidney, and lung fibroblasts) and the CMs from several prostatic carcinoma cell lines (such as parental LNCaP, PC-3, DU-145) and a bladder transitional carcinoma cell line (WH) fail to exhibit similar activity. The activity of the CM from the C4 subline cannot be substituted by GFs such as TGF-alpha, TGF-beta, bFGF, HGF, KGF, or NGF; neuropeptide (bombesin/GRP); secondary messenger analogue (dibutyryl cAMP); beta 2-adrenergic agonist (isoproterenol); or alpha 1-adrenergic agonist (phenylephrine), indicating that the factor(s) may be a novel prostate-specific autocrine factor (PSAF). Both androgen and PSAF exhibit an additive effect on up-regulating PSA gene expression, suggesting that the signal transduction pathway elicited by PSAF may differ from that mediated by the androgen receptor. Further characterization of PSAF by heat, acid, and trypsin digestion revealed that the PSAF may be a protein factor with a unique amino acid composition. These observations suggest that a novel autocrine pathway mediated by PSAF may be responsible for the overexpression of PSA mRNA and protein in a human prostatic cancer cell line. The potential clinical significance of this factor will be discussed.
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PMID:Autocrine regulation of prostate-specific antigen gene expression in a human prostatic cancer (LNCaP) subline. 768 49

Poorly differentiated MATLyLu rat prostate cancer cells are resistant to the growth inhibitory effect of transforming growth factor (TGF) beta 1 in vivo, but are inhibited by TGF-beta 1 in vitro. However, TGF-beta 1 inhibited proliferation only when the cells were plated at low density in serum-free medium (concentration for 50% of maximum inhibition, 0.1 ng/ml). TGF-beta 1 was not growth inhibitory when cells were plated at high density, or at low density in 0.5% serum. At low cell density in serum-free medium, 0.5 ng/ml TGF-beta 1 caused maximum inhibition. In the presence of basic fibroblast growth factor (10 ng/ml), TGF-beta 1 did not inhibit proliferation. In the presence of epidermal growth factor (50 ng/ml), TGF-beta 1 inhibited proliferation by only 18%. Growth inhibition by TGF-beta 1 was less effective on extracellular matrix than on plastic. The ability of high cell density, serum, growth factors, or extracellular matrix to prevent or blunt the growth inhibitory effect of TGF-beta 1 in vitro probably explains why TGF-beta 1 does not inhibit tumor growth in vivo. Thus, prostate cancer cells express high levels of TGF-beta and retain exquisite sensitivity to the growth inhibitory effect of TGF-beta, but have devised a way to protect themselves from growth inhibition by TGF-beta in vivo. TGF-beta 1 stimulated MATLyLu cell motility even at high cell density, suggesting that TGF-beta 1 might affect motility even in vivo and contribute to the aggressiveness of the tumor, without affecting proliferation.
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PMID:Modulation of transforming growth factor beta 1 effects on prostate cancer cell proliferation by growth factors and extracellular matrix. 778 Sep 74


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