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)

Morphometric analysis on two human prostate cancer cell lines (PC3 and DU-145) was carried out to better characterize these cells and to approach some problems concerning their polymorphism. In our hands, these cells appear to differ either in their ability to oxidize testosterone or in their androgen receptor content. Morphometric evaluation was performed by means of an Interactive Image Analysis System (IBAS 1), which computes several parameters related to the whole cell and to the nucleus. Our results clearly indicate that nuclear parameters alone may discriminate PC3 from DU-145 cells. Particularly, the Nuclear Roundness Factor appeared important, since it quantifies changes in nuclear shape. Nevertheless, the value of this parameter for "in vitro" morphometry may be overshadowed by the polymorphism common to the cultured cells. However, morphometric evaluation of PC3 and DU-145 cells is relevant to a better understanding and definition of the biologic nature of these cells, even if polymorphism, heterogeneity and genetic instability, specially of PC3, require further investigations.
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PMID:Morphometry of in vitro systems. An image analysis of two human prostate cancer cell lines (PC3 and DU-145). 262 79

The relative radioresponsiveness of human prostate cancer compared to malignant melanoma is well known. The effects of beta-estradiol or testosterone on the X-irradiation survival of several human cell lines were studied, including: human prostate carcinoma cell lines PC3 and DU145 and human malignant melanoma cell lines A375 and A875. Lines PC3 and DU145 demonstrated 55-61 fmol per 10(6) cells of androgen receptor with no detectable estrogen or progesterone receptor. Cells were irradiated at 120 cGy/min dose rate. There was no detectable toxicity of up to 10(-4) M testosterone or beta-estradiol on PC3 or DU145 cells in the absence of X-irradiation. At plating efficiencies from 11-13%, and plating densities of 1 x 10(4) cells per 60 cm2 flask, cell lines PC3 and DU145 demonstrated a Do of 108.5 +/- 6.5, n 2.1 +/- 0.7 cGy, and Do of 143.5 +/- 1.5 cGy, n 2.4 +/- 0.5, respectively. The addition of testosterone or beta-estradiol at 10(-4) to 10(-10) M prior to or after, X-irradiation did not alter radiosensitivity. At the same dose rate of 120 cGy/min, malignant melanoma cell lines A375 and A875 had a Do of 125 +/- 2.5 cGy, n 1.56 +/- 0.8 SF2 0.65 +/- 0.03 and line A875 demonstrated a Do of 129 +/- 4.5 cGy, n 1.58 +/- 0.4 SF2 0.55 +/- 0.04, respectively. The radiosensitivity of melanoma cell lines did not decrease at low dose rate 5 cGy/min. Thus, the in vitro radiosensitivity of androgen receptor positive prostate cancer cell lines is not necessarily altered by the presence of androgen before or after irradiation. The data support the concept that all malignant melanoma cell lines do not show a broad-shouldered cell survival curve in vitro and intrinsic cellular radioresistance.
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PMID:Radiosensitivity of human prostate cancer and malignant melanoma cell lines. 277 56

Over 600 hybridomas were derived from the immunization of mice with live cells and aqueous extracts of the human prostatic carcinoma cell line PC3. A total of 26 hybridomas with restricted reactivities were selected, subcloned and antibodies tested on a variety of tumor and normal cells. Seven monoclonal antibodies showed reactivity for prostate cancer and other tumor cell lines, including breast carcinomas. Three of the antibodies obtained after immunization with live cells reacted with live cells only and three of the four antibodies obtained after immunization with cell extract reacted with cell extracts and spent culture media. The fourth antibody in the latter group was reactive only in the immunoperoxidase staining assay. Antibody PrS5 recognized a 90,000 molecular weight molecule from 125I-surface-labeled cells in immunoprecipitation analysis. Antibodies PrE3 and PrD8 detected a nonacid glycolipid pentasaccharide from PC3 cells and meconium, and a glycoprotein of 115,000 molecular weight from 125I-surface-labeled red blood cells. The similar patterns of reactivity in RIAs and antigen analysis suggest that antibodies PrE3 and PrD8 recognize the same molecule. The results emphasize the usefulness of immunohistochemistry in the testing of monoclonal antibodies and the impact of the form in which the antigen is presented on the resultant antibody specificity.
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PMID:Monoclonal antibody-defined antigens of human prostate cancer cell line PC3. 351 28

Eight monoclonal antibodies (MAbs) raised against human prostate cancer cell lines are described. One MAb was derived from the fusion of mouse myeloma P3x63Ag8-653 cells with spleen cells of mice immunized with DU145 prostate cancer cells. The other seven were from the fusion of myeloma lines P3x63Ag8-653 or SP2/0 with spleen cells of mice immunized with PC3, DU145 and 1013L prostate cancer cells. All of the antibodies also reacted with cell lines of other human cancer types, especially carcinomas. Immunoperoxidase staining on fixed tissue revealed strong reactivity only with antibody PrN10. Seven other antibodies seemed to bind to cell surface-associated (glyco)proteins. Antibodies PrL22 and PrO11 showed similar reactivity in radioimmunoassay, and immunoprecipitated a 160 kD molecular weight polypeptide from [125I]lactoperoxidase-labeled cells. Antibodies PrHk an PrQ12 bound to molecules with apparent MW of 115 kD and 100 kD, respectively; antibodies PrM24 and PrP14 revealed a more complex picture in immunoprecipitation of surface-labeled cells.
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PMID:Shared antigens of human prostate cancer cell lines as defined by monoclonal antibodies. 388 36

The cell kinetics (percentage of cells in the S+G2 phases of the cell cycle) and the DNA ploidy levels (nuclear DNA content) were determined in 108 samples each of the PC3, DU145, and LNCaP prostate cancer models. This was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. Two to three hundred cell nuclei were analyzed for each of the 324 samples under study. The three cell lines were submitted to experimental conditions including the addition of dihydrotestosterone (DHT), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), either alone or in combination, to the culture media. The results show that under the present culture conditions, the PC3 cell line was DHT-, EGF- and bFGF-insensitive. In contrast to what is generally reported in the literature, the DU145 cell line was DHT- and EGF-sensitive under the present culture conditions, but bFGF-insensitive. The LNCaP cell line was DHT-sensitive, but EGF- and bFGF-insensitive. While mainly tetraploid, the three cell lines nevertheless exhibited a significant level of heterogeneity in their nuclear DNA content distributions. Indeed, the proportions of non-tetraploid (diploid, hyperdiploid, triploid, hypertriploid, hypertetraploid, polymorphic) DNA histograms were 14% in the PC3, 16% in the DU145, and 29% in the LNCaP cell lines. These results suggest that the DNA ploidy level would not influence the hormone sensitivity level in the cell lines since they had significantly distinct hormone sensitivity profiles while remaining mainly tetraploid.
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PMID:Influence of dihydrotestosterone, epidermal growth factor, and basic fibroblast growth factor on the cell kinetics of the PC3, DU145, and LNCaP prostatic cancer cell lines: relationship with DNA ploidy level. 747 95

We investigated the presence of interleukin 6 (IL6) receptors in human prostate carcinomas and benign prostatic hyperplasias. Interleukin 6 receptor expression was measured at the mRNA level by slot blot analysis using a probe that recognizes mRNA encoding the 80-kDa subunit of the IL6 receptor. Significant expression was found in 29 of 37 (78%) samples of benign prostate hyperplasia (BPH) and in 17 of 17 prostate carcinomas. Quantitative analysis of the expression level revealed that 11 of the 29 positive hyperplasia tissues (38%) and 4 carcinoma samples (23.5%) expressed equal or higher levels of IL6 receptor mRNA than the human hepatoma cell line PLC/PRF5, which contains about 2300 IL6 receptors per cell. We also measured IL6 receptor mRNA levels in three human prostate carcinoma cell lines LNCaP, DU145 and PC3, which are known to contain IL6 receptors because they are sensitive to the cytotoxic action of an IL6-toxin fusion protein. We were not able to detect IL6 receptor expression with the slot blot procedure, but we were able to detect IL6 receptor mRNA using a very sensitive PCR assay. Our data provide evidence that IL6 may play a role in the growth of benign and malignant prostate tumors and suggest that the IL6 receptor could be a target for the delivery of therapeutic agents in prostate cancer.
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PMID:Interleukin 6 receptor mRNA in prostate carcinomas and benign prostate hyperplasia. 751 67

The network of androgen-dependent growth factors regulating the growth and function of normal or neoplastic prostate epithelium is largely unknown. To facilitate studies directed at investigating this issue, androgen receptor-negative (AR-) PC3 prostate carcinoma cells were stably transfected with the expression plasmid CMV3 containing a constitutively active AR construct that is truncated at its hormone-binding domain (CMV-ARCA). The major characteristic of the resulting cell line (PC3-ARCA) was a growth rate approximately 35% slower than that of a control mock-transfected cell line (PC3-Neo). Of the several growth factors known to be present in the prostate, the current studies focused on the insulin-like growth factor (IGF) axis, specifically the IGF-binding proteins (IGFBPs), several of which are known to be abnormally produced by prostate cancer. Northern analysis showed that IGFBP-1 and -5 are not expressed by PC3-ARCA and -Neo cells. Western ligand and immunoblot analysis of medium conditioned by PC3-Neo and PC3-ARCA cells revealed that equal amounts of IGFBP-2, -4, and -6 were secreted. In contrast, IGFBP-3 was undetectable in the conditioned medium of PC3-ARCA cells, but normally produced by the AR- cell line PC3-Neo. IGFBP-3 disappearance from the conditioned medium of PC3-ARCA cells was transcriptionally regulated, as a marked decrement in IGFBP-3 messenger RNA was detected by S1 protection analysis. We investigated the responses of these cells to exogenously added IGF-I, IGF-II, or IGFBP-3. IGF-I and IGF-II stimulated the proliferation of PC3-ARCA cells, but not of PC3-Neo cells. IGFBP-3 had no effect when given alone. When IGFBP-3 was administered together with IGF-I or IGF-II, it further increased the mitogenic response observed in PC3-ARCA cells, but no effect on PC3-Neo cells was observed. In conclusion, our studies suggest that the presence of an active AR modulates the proliferation of transfected PC3 prostate cancer cells, and that this phenomenon occurs at least in part through the regulation of IGFBP-3 production.
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PMID:Altered growth and insulin-like growth factor-binding protein-3 production in PC3 prostate carcinoma cells stably transfected with a constitutively active androgen receptor complementary deoxyribonucleic acid. 753 76

Insulin-like growth factor I (IGF-I) seems to play an important role in prostate cell growth and its actions may be modified by IGF-binding proteins (IGFBPs) secreted by prostate epithelial cells. The IGFBP system was studied in two human prostate carcinoma cell lines, PC3 and LNCaP. Androgen receptor-negative PC3 cells secrete IGFBP-3, IGFBP-4, and IGFBP-5, as determined by immunoprecipitation of the serum-free conditioned medium with specific IGFBP antibodies. Androgen receptor-positive LNCaP cells secrete IGFBP-2 and IGFBP-3. At neutral pH, there was little or no effect of a 24-h, 37 C cell-free incubation of PC3 and LNCaP conditioned media on IGFBP. On the other hand, when media was incubated at pH 3 for 24 h, [125I]IGFBP-3 hydrolysis and the virtual elimination of endogenous IGFBP detected by Western ligand blotting were observed. This loss was not due to the acid treatment, per se, since IGFBPs remained intact if the incubation at pH 3 was carried out at 4 C. The acid-activated IGFBP protease in LNCaP and PC3 cell-conditioned media was identified as cathepsin D based on acidic pH optimum and immunoblotting. Furthermore, immunoadsorption of cathepsin D from the media attenuated the acid-activated IGFBP hydrolysis [125I]IGF-I binding to prostate cancer cells was reduced in the presence of LNCaP conditioned media that had been incubated at neutral pH for 24 h (i.e. containing intact IGFBP) but not by acid-incubated conditioned media (i.e. cathepsin D-mediated hydrolyzed IGFBP). These data indicate that prostate carcinoma cells secrete specific IGFBPs, as well as a general IGFBP protease, cathepsin D. In the proper environment, cathepsin D is capable of hydrolyzing all endogenous IGFBP and, thus, modifying IGF-I action in prostatic cells.
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PMID:Endogenous cathepsin D-mediated hydrolysis of insulin-like growth factor-binding proteins in cultured human prostatic carcinoma cells. 753 76

We report that growth of LNCaP human prostate cancer cells is significantly stimulated (up to 120% above control) by physiological estradiol (E2) concentrations. This growth increase appears to be comparable to that induced by either testosterone or dihydrotestosterone, as also reported by others. This paper presents novel illustrative evidence for estrogen-binding proteins and messenger RNA transcripts in LNCaP cells. In fact, 1) the reverse transcriptase-polymerase chain reaction system documented normal messenger RNA for estrogen receptors (ER); 2) the radioligand binding assay allowed the detection of high affinity, reduced capacity binding sites in both soluble and nuclear cell fractions; and 3) the immunocytochemical analysis showed a consistently intensive staining for both ER and progesterone receptors. Compared to other human estrogen-responsive mammary cancer cells, MCF7 and ZR75-1, ER expression in LNCaP cells was not significantly lower, as shown by levels of the ER transcripts, number of sites per cell, or femtomoles per mg DNA as well as the percentage and intensity of immunocytochemical staining. A relative estimate of ER expression obtained by matching LNCaP with another human prostate cancer cell line, PC3, always displayed significantly and consistently higher levels in LNCaP cells. The detection of relatively high type I ER content in either cell compartment of LNCaP cells was paralleled by a highly intensive staining for progesterone receptors. In addition, evidence that the synthetic androgen R1881 did not compete for type I binding of E2 and that any E2-induced growth was completely reversed by the pure antiestrogen ICI-182,780, but unaffected by the antiandrogen Casodex, clearly suggests that the biological response of LNCaP cells to E2 is mediated via its own receptor.
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PMID:Growth of LNCaP human prostate cancer cells is stimulated by estradiol via its own receptor. 753 68

Androgens are required for the optimal growth and development of both the normal prostate and steroid-sensitive prostate cancer. PC3 prostate cancer cell lines stably expressing the human androgen receptor (AR) and possessing an androgen-sensitive phenotype (PC3-hAR) were used to examine the role of the epidermal growth factor receptor (EGFR) in androgen-stimulated prostate cancer cell growth. Epidermal growth factor (EGF) and dihydrotestosterone (DHT) independently induced the growth of PC3-hAR cells. Moreover, EGF and DHT in combination exerted a synergistic effect on PC3-hAR cell growth. DHT-exposed PC3-hAR cells expressed a greater than 2-fold increase in EGFR mRNA and 50% more EGFR protein than controls. Time course radioligand-binding assays confirmed these findings by showing an elevation in EGF binding in the DHT-exposed PC3-hAR cells. In addition, radioligand competition-binding studies revealed a 2-fold increase in EGFR-EGF binding affinity in the PC3-hAR cells after DHT treatment. However, no enhancement of transforming growth factor alpha or EGF expression was detected because DHT did not affect the levels of these cytokines in the PC3-hAR cell lysate or conditioned media. Our observations suggest that DHT increases both EGFR number and receptor-ligand affinity in androgen-sensitive prostate cancer cells and that these effects correlate with increased EGF binding and an enhanced mitogenic response to EGF.
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PMID:Androgen up-regulates epidermal growth factor receptor expression and binding affinity in PC3 cell lines expressing the human androgen receptor. 760 41


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