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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have identified and characterized a novel human insulin-like growth factor I (IGF-I) precursor from the transplantable T61 human breast cancer xenograft and from normal liver. The mRNA encoding this precursor contains a 5'-untranslated region that is 83% identical to the corresponding region of a previously described variant rat IGF-I. The nucleotide sequence of the cloned cDNA predicts an IGF-IA protein precursor of 137 amino acids, including a 32 residue signal peptide, 70 amino acid IGF-I, and a 35 residue COOH-terminal extension or E peptide. The exon encoding this variant maps in the genome between IGF-I exons 1 and 2, in a similar location to the homologous rat exon 1a. The rat and human exons 1a are 59% identical over 1443 nucleotides, with DNA sequence conservation occurring in a mosaic pattern. Human IGF-I mRNAs encoding this novel exon are expressed in liver, T61 tumor cells, and in an ovarian carcinoma cell line, NIH OVCAR3. These studies demonstrate that as in the rat, the human IGF-I gene contains six exons that are variably processed into multiple IGF-I mRNAs. The mechanisms responsible for generating different IGF-I mRNAs thus appear to be conserved among mammalian species.
Mol Endocrinol 1990 Dec
PMID:A novel human insulin-like growth factor I messenger RNA is expressed in normal and tumor cells. 208 90

Previous studies from our laboratory have demonstrated that OVCA 433 human ovarian carcinoma cells are glucocorticoid responsive by several criteria and contain high affinity, saturable, steroid-specific glucocorticoid receptors. These cells secrete both mammalian plasminogen activators (PAs), urokinase (uPA) and tissue-type PA (tPA). Treatment of OVCA 433 cells with 1 x 10(-7) M dexamethasone (Dex) for 4 days led to 77% and 83% reductions in the extracellular activities of uPA and tPA, respectively, released into serum-free conditioned medium during a 1-h period. Dex treatment led to a 71% decrease in the rate of extracellular uPA antigen accumulation, as determined by enzyme-linked immunosorbent assay, as well as a 73% reduction in steady state uPA mRNA levels. In contrast, Dex treatment led to only a 42% decrease in the rate of extracellular tPA antigen accumulation and a 48% decrease in tPA mRNA levels; such decreases were insufficient to account for the 83% reduction in tPA activity. Thus, while Dex-induced decreases in uPA antigen and mRNA levels accounted for all but 6% of the decrease in uPA activity, a large discrepancy existed between the magnitudes of decreased tPA activity and decreased tPA antigen and mRNA levels. OVCA 433 cells produce both PAI-1 and PAI-2, two specific PA inhibitors. Treatment of cells with 1 x 10(-7) M Dex for 4 days led to a 3.3-fold increase in the rate of extracellular PAI-1 accumulation, with little or no effect on PAI-2 accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1989 Jun
PMID:Different mechanisms contribute to simultaneous inhibition of urokinase and tissue-type plasminogen activators by glucocorticoids in human ovarian carcinoma cells. 250 May 90

Activation of ras genes in human ovarian carcinomas and ovarian carcinoma cell lines was tested by transfection of NIH 3T3 cells with high molecular weight DNA extracted from fresh tumors or from cell lines. Of 18 ovarian tumors and tumor cell lines that were exhaustively tested, only one yielded DNA active in focus-induction in this assay. Southern blot analysis of DNA in serially transformed NIH 3T3 foci revealed restriction fragments that hybridized with a probe specific for the human N-ras oncogene and with human repetitive (Alu) sequences. Individually transformed foci contained N-ras hybridizing fragments of different sizes. Northern blots of RNA extracted from different transformants revealed the expression of different transcripts hybridizing with the N-ras probe. The transformants also expressed a 700 base RNA that hybridized with a human B-lym probe. The low prevalence of ras activation in ovarian tumors as measured by transforming capability suggests that ras activation does not play an important role in the development of most human ovarian tumors.
Mol Biol Med 1987 Oct
PMID:Evidence against ras activation in human ovarian carcinomas. 332 Jun 75

We have investigated the role of glutathione in determining the macromolecular binding and cytotoxicity of cisplatin (DDP) and melphalan (LPAM) in human ovarian carcinoma cells and DDP-resistant L1210 mouse leukemia cells. Glutathione reacted avidly with DDP in normal saline with a bimolecular rate constant of 16.2 M-1 hr-1. Glutathione had no effect on the rate of hydrolysis of LPAM, consistent with the SN1-like reaction mechanism of LPAM. Glutathione protected calf thymus DNA and bovine serum albumin from DDP platination and LPAM alkylation. Glutathione also protected nuclei isolated from human ovarian carcinoma cells from DDP platination. The importance of intracellular glutathione in determining the cytotoxicity of DDP and LPAM was assessed by depletion of glutathione with buthionine sulfoximine in three cell types. Exposure to 0.5 mM buthionine sulfoximine for 20-28 hr depleted glutathione to levels that were 10-20% of control levels. COLO 316 and 2008 human ovarian carcinoma cells, and ZCR9 mouse leukemia cells were all sensitized to LPAM cytotoxicity by this level of glutathione depletion. The dose modification factors, defined as the IC50 control cells/IC50 depleted cells, were: 2.6 +/- 0.5 for COLO 316 cells, 1.6 +/- 0.1 for 2008 cells, and 2.1 +/- 1.1 for ZCR9 cells. In contrast, glutathione depletion had a minimal effect on DDP cytotoxicity in these cells with dose modification factors of: 1.2 +/- 0.2 for COLO 316 cells, 0.8 +/- 0.3 for 2008 cells, and 1.1 +/- 0.1 for ZCR9 cells. The differential potentiation of DDP and LPAM cytotoxicity by glutathione depletion in these cells, despite the similar protection that glutathione affords macromolecules from drug binding, suggests that there are fundamental differences in the intracellular interaction of these electrophilic drugs with glutathione.
Mol Pharmacol 1986 Dec
PMID:Differential sensitization of human ovarian carcinoma and mouse L1210 cells to cisplatin and melphalan by glutathione depletion. 378 41

A phage-display combinatorial library of VL and VH sequences of mouse antibodies was constructed, which contained 4.5 x 10(7) independent clones. From this library pools of phage were selected by up to four biopanning rounds on cytoskeletal preparations of ovarian carcinoma cells (OVCAR-3). Phage of these pools were then allowed to bind to a cytoskeleton preparation of bladder carcinoma cells (T24). The binding phage were challenged by a monoclonal antibody (mAb) directed against an epitope on cytokeratin 8. Displaced phage were rescued and screened for anti-cytokeratin immunoreactivity by ELISA, indirect immunofluorescence and Western blotting. About 50% of the phage selected by competition with the cytokeratin mAb reacted with the cytoskeletal preparations of T24 cells in ELISA. In contrast, in non-cytokeratin-containing cells, no reaction was observed. Immunofluorescence and Western blotting studies with a number of these clones showed reactivity against cytokeratin. We conclude that the phage-display competitive elution method can be used as a rapid technique to obtain immunoreactive phages, and eventually single-chain Fv (scFv) antibodies directed against defined epitopes, which were formerly characterized and validated by mAbs.
J Mol Biol 1994 Dec 09
PMID:Selection of phage-displayed antibodies specific for a cytoskeletal antigen by competitive elution with a monoclonal antibody. 752 64

The cytokine interleukin-1 alpha (IL-1 alpha) showed a cytostatic effect on human ovarian carcinoma cells and significantly enhanced the antiproliferative activity of cis-diamminedichloroplatinum(II) (cisplatin) toward the NIH:OVCAR-3 tumor cell line in culture. The factor of sensitization was 15-20-fold. The maximum levels of sensitization were observed both with simultaneous exposure to cisplatin and IL-1 alpha and with 24-hr pretreatment with IL-1 alpha. Synergy between these agents was diminished when cells were pretreated with an IL-1 alpha-specific receptor antagonist, indicating that synergistic interaction was receptor mediated. Using atomic absorption spectroscopy, we evaluated the cellular accumulation of cisplatin and the DNA platination; the results showed that IL-1 alpha increased cellular accumulation of cisplatin and DNA platination. Cisplatin did not affect IL-1 alpha accumulation in NIH:OVCAR-3 cells. Further studies showed that IL-1 alpha reduced the removal of platinum from DNA. These results strongly suggest that IL-1 alpha inhibits DNA repair, and this decrease in DNA repair may explain, in part, the strong synergistic interaction between IL-1 alpha and cisplatin in NIH:OVCAR-3 cells.
Mol Pharmacol 1995 Jun
PMID:Effects of interleukin-1 alpha on DNA repair in human ovarian carcinoma (NIH:OVCAR-3) cells: implications in the mechanism of sensitization of cis-diamminedichloroplatinum(II). 760 68

The factor(s) which regulate the rapid growth of ovarian epithelial carcinoma, as well as other types of malignant tumors, are still largely unknown. Recently, experimental evidence indicated that neoplastic cells are able to synthesize peptide growth factor and their receptors. This autocrine secretion could be one of the mechanisms to sustain their abnormal proliferation. In this study, we evaluated the possible role of basic fibroblast growth factor (bFGF) that is a likely candidate because it has both angiogenic and mitogenic activity and has been found in a variety of other neoplasms. As assessed by both bioassay and radioimmunoassay, a bFGF-like protein was present in seven ovarian epithelial neoplasms and in primary culture of dispersed ovarian cancer cells. Levels of this protein as well as its bioactivity varied in the different tumors examined. Reverse transcription-polymerase chain reaction indicated that the genes for bFGF and its receptor are expressed in all the samples studied. These data suggest that bFGF might be one of the growth factor regulating ovarian cancer cell proliferation through an autocrine mechanism. We are currently investigating whether the expression of this growth factor varies as a function of the histologic grade of the tumors.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Basic fibroblast growth factor and ovarian cancer. 762 84

The effects of 17 beta-estradiol (E2) on the growth and the levels of estrogen receptor (ER), progesterone receptor (PR) and pS2 protein were examined in a range of 8 ovarian carcinoma cell lines. E2 stimulated growth of the 3 cell lines with an ER content of 80-220 fmol/mg protein but not the 5 cell lines with ER concentrations less than 20 fmol/mg protein. After exposure to E2, ER concentration in 2 of the 3 responsive cell lines was decreased relative to untreated cells and in 2 lines, progesterone receptors were increased. No change in steroid receptor levels was observed in cell lines with low or negligible levels of receptors. The pS2 protein was not induced by E2 in the 5 ovarian carcinoma cell lines examined. These results indicate that E2 can stimulate the growth of some ER-positive ovarian carcinoma cells and that these effects may be associated with changes in the cellular levels of steroid hormone receptors.
J Steroid Biochem Mol Biol 1994 Aug
PMID:The regulation of growth and protein expression by estrogen in vitro: a study of 8 human ovarian carcinoma cell lines. 804 41

A novel cDNA clone was isolated using a polyclonal serum directed against partially purified ovarian carcinoma antigen CA125. The deduced peptide sequence lacked membrane protein characteristics expected for CA125 but encompassed a B-box/coiled coil motif present in many genes with transformation potential. The gene was mapped by fluorescence in situ hybridization within the minimum region known to contain the familial breast/ovarian carcinoma gene, BRCA1. YAC and cosmid clones were isolated and used to refine the location of this gene adjacent and proximal to the RNU2 locus. The exon structure of the gene was determined. Extensive SSCP and sequence analysis of over 100 tumour and normal DNAs from familial and sporadic breast cancers and sporadic ovarian cancers failed to detect mutations in the coding region of this gene.
Hum Mol Genet 1994 Apr
PMID:A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. 806 4

We have previously shown that, in mouse NIH/3T3 cells, it is necessary to coexpress the gene for human hepatocyte growth factor/scatter factor (HGF/SFhu) with its receptor, the human met protooncogene (methu), to activate the transforming activity of the receptor (S. Rong, M. Bodescot, D. Blair, T. Nakamura, K. Mizuno, M. Park, A. Chan, S. Aaronson, and G. F. Vande Woude, Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that exceptionally high levels of the ligand and its receptor are expressed in tumor cell explants after several tumor passages through nude mice. Confluent tumor cells explanted after the second passage in nude mice can express 1700 units/ml/10(6) cells/72 h of scatter activity as determined in Madin-Darby canine kidney cell scatter assays. The motogenic factor produced by these cells is easily purified by heparin-Sepharose chromatography, and the purified factor efficiently induces tyrosine phosphorylation of Methu in YaOvBix2NMA human ovarian carcinoma cells. To account for the unusually high level of HGF/SFhu and Methu expression, we propose that normal levels of Methu receptor are inefficient at transducing the signal(s) required for transformation of mouse cells. Therefore, high levels of Methu receptor are required for tumorigenesis, and corresponding high levels of the ligand are required to induce the signal. Consistent with this model, endogenous mouse scatter factor is not detected in conditioned medium from cells transformed by overexpression of the Metmu receptor.
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PMID:Tumorigenesis induced by coexpression of human hepatocyte growth factor and the human met protooncogene leads to high levels of expression of the ligand and receptor. 839 96


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