Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that the monoclonal antibody KR-P8 detects a prostate organ-specific antigen that is distinct from other markers such as prostatic acid phosphatase and prostate specific antigen. In this report we demonstrate that the antigen recognized by KR-P8 is among the secretory products of both normal and malignant prostatic epithelium. Immunoperoxidase staining patterns showed that the antigen was concentrated on the luminal surfaces of the glandular epithelial cells of prostate, and also that the antigen was localized within secretory vacuoles of cells of the prostate tumor line PC3. In addition, using an immunoblotting assay the KR-P8 binding antigen was detected in the growth media of PC3 cells and also found to be present in human urine and seminal plasma. The data suggest that the antigen recognized by KR-P8 may be a useful marker for studying the secretory processes of the prostate gland.
 ...
PMID:Localization of a normal prostatic secretory product using the monoclonal antibody KR-P8. 241 Jun 35

The KR-P8 monoclonal antibody identifies an organ-specific antigen that is associated with normal as well as malignant specimens of human prostate tissue. The antigen is secreted by cells of the prostate and is present in samples of seminal plasma. Data presented here describe the biochemical nature of the antigen that is recognized by KR-P8 as it occurs in seminal plasma and in extracts prepared from cells of the prostate tumor line, PC3. Antigen contained in seminal plasma migrated as a broad band on SDS-polyacrylamide gels in the molecular weight range of 48,000-75,000 d. A similar pattern was observed for antigen prepared from detergent extracts of PC3 cells. The antigen was found to be sensitive to treatment with trypsin and chymotrypsin and the contribution of carbohydrate residues to the structure of the molecule was shown by studies that demonstrated binding of the antigen to Concanavalin A and Soybean Agglutinin lectins. Loss of antigenicity subsequent to periodate oxidation suggested that carbohydrate units are involved in the recognition site for KR-P8 on the antigen.
 ...
PMID:Biochemical nature of the prostate-associated antigen identified by the monoclonal antibody, KR-P8. 242 89

Transforming growth factor beta (TGF beta) exerts a wide spectrum of activity on many different cell types. Since TGF beta inhibits the growth of a variety of epithelial tumor cells in vitro, we examined the effects of TGF beta on the human prostate cancer cell lines DU145, PC3 and LNCaP for possible inhibitory activity. Growth in monolayer was initially inhibited in a dose-response fashion in the two androgen-independent cell lines, PC3 and DU145 but not in the androgen-dependent LNCaP cells. The rate of growth of the PC3 and DU145 cells treated with TGF beta, however, eventually returned to control levels despite retreatment with TGF beta. Anchorage-independent growth was inhibited to 55% and 16% control levels in PC3 and DU145, respectively. Scatchard analysis showed 1500 and 2900 TGF beta binding sites/cell on DU145 and PC3 cells with Kd = 6.9 and 12 x 10(-12) M, respectively. High-affinity binding could not be demonstrated on LNCaP cells. We also explored the possibility that TGF beta was secreted by these cells. Analysis of conditioned media by immunoprecipitation and a radioreceptor assay showed secretion of TGF beta into the media by DU145 and PC3 but not by LNCaP. Northern analysis showed the presence of TGF beta mRNA in DU145 and PC3, but not in LNCaP. These data indicate that TGF beta might serve as an autocrine inhibitory factor in prostate cancer. In addition, because TGF beta affects a wide range of cell types, TGF beta production by prostate cancer cells may contribute an important paracrine function in the development of tumor stromal tissue and metastases.
 ...
PMID:Differential effects of transforming growth factor beta on human prostate cancer cells in vitro. 254 87

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.
 ...
PMID:Monoclonal antibody-defined antigens of human prostate cancer cell line PC3. 351 28

Of four tumor cell lines, the murine YAC lymphoma, the human K562 lymphoma, and the human prostatic carcinomas PC3 and PC93, the susceptibility to murine natural killer (NK) cells as well as the tumorigenicity in young (3.5-4 weeks old) and in adult (8-10 weeks old) nude mice were studied. In young nude mice, which exhibited a lower level of NK cell activity than adult nude mice, the formation of solid tumors after inoculation of tumor cell suspensions occurred more frequently and with a shorter time lag than in adult animals. These effects were observed not only with the NK-sensitive YAC cells, but also with the relatively NK-insensitive PC3 and PC93 cells, indicating that also factors other than NK cell susceptibility may influence the growth of tumor cells in nude mice. Therefore, the use of young nude mice may enhance the rate of success of heterotransplantation of human tumors, regardless of the NK cell susceptibility of the tumor cells.
 ...
PMID:Growth of tumor cells with different sensitivities for murine natural killer cells in young and adult athymic nude mice. 396 94

The culture media of three cell lines, a human prostate carcinoma (PC3), a rat Leydig cell tumor (Rice-500), and a rat carcinosarcoma (WRC-256), that were derived from tumors associated with humoral hypercalcemia of malignancy (HHM), were examined for stimulation of adenylate cyclase in ROS 17/2.8 osteoblastic cells and for bone resorptive activity in culture. Cells from a nonhypercalcemic variant of the WRC256 tumor served as control. Extracts from three solid human tumors, a lung adenocarcinoma from a patient with HHM and two adenocarcinoma from normocalcemic patients (lung and colon), were also examined for adenylate cyclase stimulation. We found excellent correlation between stimulation of cyclic AMP accumulation in ROS 17/2.8 cells and bone resorbing activity in culture, or production of HHM in vivo. Stimulation of adenylate cyclase by HHM factors was inhibited by the parathyroid hormone competitive inhibitor, [8norleucyl, 18norleucyl, 34tyrosinyl] bovine parathyroid hormone (3-34) amide.
 ...
PMID:Factors associated with humoral hypercalcemia of malignancy stimulate adenylate cyclase in osteoblastic cells. 668 37

A dominant negative H-ras mutant, N116Y, was transfected into a variety of human tumor cell lines. N116Y extremely inhibited the proliferation of A431 (vulva), PC3 (prostate), T24 (bladder), MCF7 (breast), NKPS and TMK1 (stomach) cancer cell lines. A431 and PC3 cells were particularly susceptible to N116Y. In order to examine the effects of N116Y on the neoplastic phenotypes, we transfected a less efficient N116Y expression vector into A431 cells. Almost all clones survived after G418 selection. However, they did not retain the N116Y gene and only one clone faintly expressed N116Y. This N116Y-expressing clone had no tumorigenicity in vivo, and revealed deformed morphology and DNA fragmentation, suggesting that N116Y might have induced apoptotic cell death. Thus, N116Y may be applicable for gene therapy of a wide spectrum of human tumors.
 ...
PMID:Suppression of various human tumor cell lines by a dominant negative H-ras mutant. 758 6

Suramin, a polyanionic naphthylurea, represents a novel class of antineoplastic drugs with a variety of activities against tumor cell proliferation. However, its clinical use is hampered by serious toxicity. To gain more insight into structure-activity relationships of suramin, we investigated the antiproliferative action of suramin and 19 suramin analogues in vitro using 5 different human cell lines (HT29, MCF7, SW13, PC3, and T47D). In addition, for seven analogues the angiostatic potential with and without hydrocortisone was assessed using a modified chorioallantois membrane assay. Only the symmetric compounds exhibited antiproliferative action in vitro; several analogues were more active than suramin (e.g., NF031, NF037, NF326). Suramin analogues with six sulfonic acid groups showed a wide range of activity in HT29 cells (IC50 = 43-390 microM), indicating that besides the polyanionic feature, other structural elements are important (e.g., stiffness of the bridge between the two terminal naphthyl rings). Some of the smaller ureas with only four sulfonic acid groups retained significant antiproliferative activity. Compounds active in cell lines also inhibited angiogenesis in the chorioallantois membrane assay, suggesting a similar mode of action. Hydrocortisone increased the angiostatic effect of most but not all of the screened suramin analogues. These findings may guide the use of suramin analogues for improved antitumor therapy in vivo.
 ...
PMID:Antiproliferative and angiostatic activity of suramin analogues. 758 36

The tyrosine kinase substrate p120cas (CAS), which is structurally similar to the cell adhesion proteins beta-catenin and plakoglobin, was recently shown to associate with the E-cadherin-catenin cell adhesion complex. beta-catenin, plakoglobin, and CAS all have an Arm domain that consists of 10 to 13 repeats of a 42-amino-acid motif originally described in the Drosophila Armadillo protein. To determine if the association of CAS with the cadherin cell adhesion machinery is similar to that of beta-catenin and plakoglobin, we examined the CAS-cadherin-catenin interactions in a number of cell lines and in the yeast two-hybrid system. In the prostate carcinoma cell line PC3, CAS associated normally with cadherin complexes despite the specific absence of alpha-catenin in these cells. However, in the colon carcinoma cell line SW480, which has negligible E-cadherin expression, CAS did not associate with beta-catenin, plakoglobin, or alpha-catenin, suggesting that E-cadherin is the protein which bridges CAS to the rest of the complex. In addition, CAS did not associate with the adenomatous polyposis coli (APC) tumor suppressor protein in any of the cell lines analyzed. Interestingly, expression of the various CAS isoforms was quite heterogeneous in these tumor cell lines, and in the colon carcinoma cell line HCT116, which expresses normal levels of E-cadherin and the catenins, the CAS1 isoforms were completely absent. By using the yeast two-hybrid system, we confirmed the direct interaction between CAS and E-cadherin and determined that CAS Arm repeats 1 to 10 are necessary and sufficient for this interaction. Hence, like beta-catenin and plakoglobin, CAS interacts directly with E-cadherin in vivo; however, unlike beta-catenin and plakoglobin, CAS does not interact with APC or alpha-catenin.
 ...
PMID:The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. 765 99

N- and K-ras mutations at codons 12 and 13 were investigated using oligonucleotide hybridization analysis after PCR amplification and subsequent sequence analysis of the amplified DNA from the region of interest in the following prostatic primary and metastatic (met) carcinoma-derived cell lines: 1013L (primary), PC3 (bone met), DU145 (brain met), and LNCaP (lymph node met). We also examined fresh and archival primary and metastatic prostate tumor tissue and benign prostatic hypertrophy specimens. All prostatic cells and tissues examined contain at least one wild-type N- and K-ras allele with respect to codons 12 and 13. No mutations were found at N-ras codon 13. The only mutation seen in the prostatic cell lines and tissues was a K-ras codon 12 position II G-to-T transversion. Since these are established nonclonal cell lines that have adapted to tissue culture, it is possible that this mutation does not represent the mutational state of prostatic carcinoma in vivo. However, the lack of consistent mutation in the ras genes amplified directly from tumors suggests that when ras mutations occur during the progression of prostatic carcinoma, they are late-stage events not directly involved in the initial development of disease. Immunoprecipitation studies using pan-ras antibodies revealed no evidence of altered expression of Ras proteins.
 ...
PMID:Mutational status of codons 12 and 13 of the N- and K-ras genes in tissue and cell lines derived from primary and metastatic prostate carcinomas. 842 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>