Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amplification and expression of the cellular oncogene c-Ki-ras have been detected in twelve tissue specimens of human ovarian adenocarcinoma, one ascites of ovarian cancer and ovarian cancer cell line NIH: OVCAR-3. Four out of the twelve cancer tissue specimens, one specimen of cancer ascites cells and the NIH: OVCAR-3 cancer cell line showed elevated amplification of c-Ki-ras, as compared to the human fibroblast cell line FS4 and normal ovarian tissues. The amplification of the c-Ki-ras gene showed some correlation with clinical stages of ovarian cancer. The levels of c-Ki-ras specific RNA transcripts and ras gene product p21 were also elevated in these four cancer tissue specimens. Surprisingly, a discrepancy between amplification and expression of c-Ki-ras was noted in five of the other eight cancer tissue specimens, in which enhanced expression of c-Ki-ras was present without the accompanying elevated amplification of c-Ki-ras. The results do provide some clues to understanding the possible mechanisms of tumorigenesis in human ovarian cancer.
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PMID:Amplification and expression of c-Ki-ras oncogene in human ovarian cancer. 169 86

To detect mutationally activated ras oncogenes, we analyzed electrophoretic mobilities of ras p21 proteins utilizing the fact that many ras oncogenes produce abnormal p21 proteins that migrate at SDS/polyacrylamide gel electrophoresis as a fast-moving or slow-moving species in comparison to a normal p21 depending on the kind of mutation. Of 18 human tumor cell lines analyzed, four (SW480, SW620 and SW403 colon cancers, and SW626 ovary cancer) produced p21 belonging to the slow-moving species, suggesting a point mutation within codon 12 of a member of the three ras genes, H-, Ki- and N-ras. Subsequent DNA transfection analysis using NIH/3T3 cells as recipients identified activated Ki-ras oncogenes in the same four but not in other 14 cell lines. Thus, the analysis of p21 might serve as a rapid primary method to screen a large number of tumor materials for the presence of certain types of mutationally activated ras oncogenes.
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PMID:Detection of ras oncogenes by analysis of p21 proteins in human tumor cell lines. 306 79

The monoclonal antibody RAP 5 immunoreactive with the ras gene product p21 was used in an immunohistochemical study of 57 patients with advanced ovarian cancer and in 28 normal ovaries. The pattern of the staining of various tumor specimens was similar to the germinal epithelium of normal ovaries, whereas the intensity of staining was more enhanced in carcinomas than in normal ovaries. However, we found a lack of correlation among staining intensity of RAP 5 and the histologic type, the histologic grade, the ploidy class, and the clinical outcome.
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PMID:Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome. 327 89

The growth-inhibitory protein p21WAF1/CIP1 is a potent inhibitor of various cyclin-dependent kinases, the expression of which is regulated at the transcriptional level by p53-dependent and -independent mechanisms. We examined p21WAF1/CIP1 mRNA and protein expression in 5 human ovarian-adenocarcinoma cell lines, 1 primary culture of normal surface epithelium and 17 human ovarian-tumor specimens. In culture cells, the p21WAF1/CIP1 protein was expressed in normal ovarian epithelial cells and at a high level in the adenocarcinoma 2008 and IGROV-1 cell lines. p21 WAF1/CIP1 expression was undetectable at the mRNA and protein levels in the NIH-OVCAR-3 and SKOV-3 ovarian-adenocarcinoma cell lines which are respectively mutated and deleted in the p53 gene. Heterogeneous expression of p21WAF1/CIP1 observed in ovarian-cancer cell lines in culture was also found in vivo on tumor specimens. p21WAF1/CIP1 expression is undetectable in 25% of the ovarian biopsies examined. Since it has been found that the p53 gene is mutated in 79% of ovarian cancer, the absence of p21WAF1/CIP1 expression in 25% of these ovarian cancer could not be correlated with p53 mutation. The proliferation index of the 17 tumors showed great variation from one tumor to another. However, no significant correlation was found between p21WAF1/CIP1 expression and the proliferation rate of the tumors.
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PMID:Expression of p21WAF1/CIP1 is heterogeneous and unrelated to proliferation index in human ovarian carcinoma. 759 Dec 74

Epithelial ovarian cancer probably occurs due to activation of several different combinations of genes, which produce cancers that vary biologically and clinically. We tested this hypothesis in 100 consecutive ovarian carcinomas by molecular biology techniques at the DNA and protein levels in three genes (erbB-2, myc, ras), which are frequently altered in this tumor system. Abnormally high expression of erbB-2 gene encoded p185 protein was observed in 31% of the samples, while erbB-2 gene amplification was detected by Southern analysis in 8%. ErbB-2 abnormal gene expression did not significantly affect the clinical outcome of patients, conferring a marginal worsening of survival. In 25 out of 96 (26%) tumor samples there was myc amplification. Higher levels of the ras-encoded p21 protein than in normal ovaries and benign ovarian tumors were found in 45% of the samples. Simultaneous overexpression of p185 and p21 was associated with shorter disease free (p = 0.02) and overall survival (p = 0.04) at significance levels notably higher than those observed for these oncoproteins singly. In addition, survival of patients with myc amplification and high p185/p21 coexpression was significantly worse (p < 0.05) than that of patients with normal levels. Our data suggest that concurrent abnormal gene expression may act synergistically to endow ovarian tumor cells with a highly aggressive phenotype. Evaluation of these genes may be helpful in the biological characterization of ovarian cancer and in defining individual patient prognosis.
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PMID:Concurrent abnormal expression of erbB-2, myc and ras genes is associated with poor outcome of ovarian cancer patients. 765 38

We introduce a new epithelial ovarian carcinoma cell line (UCI 107) from a patient with papillary adenocarcinoma of the ovary who had not been previously treated. The growth characteristics, chemosensitivity, tumorgenicity, cytogenetics, antigen expression, and receptor status were examined. A standardized photometric assay was implemented to determine the response to single drug agents including doxorubicin (ADR), cisplatin (CDDP), and Taxol. Tumorgenicity was determined utilizing female athymic mice implanted either subcutaneously (sc) or intraperitoneally (ip) with 1 x 10(7) UCI 107 cells. UCI 107 cells grow rapidly in culture with lag phase of approximately 48 hr, population doubling time of 24-36 hr, and saturation density of 4.8 x 10(5) cells/cm2. The 50% inhibitory concentration values for the chemotherapeutic agents were 0.170, 0.029, and 0.330 microM for ADR, Taxol, and CDDP, respectively. Nude mice produced ip tumors within 15 days, resulting in death from carcinomatosis 40-45 days postimplantation. Subcutaneous tumor nodules (100 mm3) were observed in nude mice 12-13 days post-tumor implantation reaching a maximum tumor volume of approximately 10,000 mm3 by Day 30. The cytogenetic composite karyotype is as follows: 46, X, der (X) t (X;7) (p11;q22), inv dup (1) (q12;q32), t (6;6;11;22) (p21.3;q16;q23.3;q13.3), del (13) (q14.1). The cell line expresses progesterone receptor, increased levels of p53 protein, and cytokeratins. It does not appear to express Her-2/neu protein, estrogen receptor, nor the CA 125 tumor marker. In conclusion, UCI 107 displays unique cellular properties which make it an attractive model for the study of ovarian cancer.
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PMID:Characterization and development of UCI 107, a primary human ovarian carcinoma cell line. 767 98

Transforming growth factor beta (TGF beta) is an important regulator of cellular proliferation. In normal ovarian epithelial cells, TGF beta acts to inhibit growth. However, in ovarian cancer cell lines, this effect is usually lost. Although the regulatory pathway of TGF beta remains unclear, TGF beta-treated cells arrest late in G1. This inhibition appears to involve blocking of the cyclin-dependent kinase phosphorylation of the retinoblastoma protein. Recently, a general inhibitor of cyclin-dependent kinases, CIP1/WAF1/p21, was identified. Expression of CIP1 is positively regulated by binding of wild-type p53 to a consensus response element upstream of the CIP1 gene. Overexpression of the CIP1 protein causes growth suppression, analogous to TGF beta and wild-type p53. We have examined the induction of CIP1 by TGF beta 1 in ovarian cancer cell lines that have been previously characterized for their proliferative response to TGF beta 1. OVCA420, a cell line that is dramatically growth inhibited by TGF beta 1, significantly induced CIP1 expression in response to TGF beta 1. CIP1 induction was accompanied by a decrease in cdk2 kinase activity and cdk2 protein levels. In three other cell lines that respond weakly to TGF beta 1, CIP1 expression was not induced. To determine if TGF beta 1 induction occurs via p53, regulation of p53 RNA and protein was examined. No differences in p53 transcription, steady-state protein level, de novo synthesis, phosphorylation, or subcellular accumulation were noted. Furthermore, TGF beta 1 could not induce transcription from a consensus p53 DNA binding site in the TGF beta 1-response cell line.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor beta 1 can induce CIP1/WAF1 expression independent of the p53 pathway in ovarian cancer cells. 769 78

The expression of cyclins, cyclin-dependent kinases (cdk), and cdk inhibitors was evaluated in clones from a human ovarian cancer cell line transfected with a temperature-sensitive mutant of p53, after treatment with the anticancer agents doxorubicin (DX) and AMSA. The two drugs were selected on the basis of their activity in these clones, since AMSA is equally active in cells expressing mutated or wild-type (wt) p53, while DX was much less cytotoxic in cells expressing wt p53. In untreated cells, the expression of wt p53 induced an accumulation of cells in the G2 and perhaps also the G1 phase of the cell cycle. Concomitantly cyclin B1 and cdc2 increased. Cyclin E and particularly D1 levels were also raised by wt p53 expression. Treatment of mutated p53-expressing cells (SK23a cells kept at 37 degrees C) with DX or, more so, with AMSA, resulted in a strong accumulation of cyclin B1 and cdc2, in accordance with their ability to block cells in G2 phase of the cell cycle. Wt p53-expressing cells (SK23a cells kept at 32 degrees C) treated with the drugs showed an increase in p21 expression and consequently decreased kinase activity after immunoprecipitation with p21 antibodies. Cdc2-associated kinase activity was also reduced in these conditions. We could also observe a decrease in the percentage of cells in G1 and G2 phases and an accumulation of cells in S phase after both DX and AMSA. Cdk2, retinoblastoma, and p27 levels did not change significantly. Treatment with DX or AMSA caused similar effects, suggesting that p53-induced changes in cyclin, cdk, and cdk inhibitors after DNA damage are not responsible for the marked reduction in the cytotoxicity of DX we observed in wt p53-expressing cells.
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PMID:Changes in cyclins and cyclin-dependent kinases induced by DNA damaging agents in a human ovarian cancer cell line expressing mutated or wild-type P53. 883 77

The cell cycle regulatory proteins p16 and p21 cause cell cycle arrest at the G1 checkpoint by inhibiting activity of cyclin D-CDK4 complexes. The TP53 gene, regulating the p21 protein, is mutated at high frequency in ovarian cancer. The CDKN2 gene, encoding the p16 protein, has been mapped to chromosome 9p21 and encompasses three exons. To establish the frequency of CDKN2 gene abnormalities in ovarian tumour specimens, we have studied this gene in five ovarian cancer cell lines and in 32 primary and five metastatic ovarian adenocarcinomas. Using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequencing techniques both exon 1 and 2 of the CDKN2 gene, encompassing 97% of the coding sequence, were analysed. In addition, the TP53 gene was studied for the presence of mutations. The cell line HOC-7 showed a 16 bp deletion in exon 2 of the CDKN2 gene, resulting in a stop codon, whereas in cell line SK-OV-3 this gene was found to be homozygously deleted. Nine primary tumour specimens showed a migration shift on SSCP. Sequencing revealed a common polymorphism (Ala148Thr) in seven of these ovarian tumour specimens. The two other tumour samples were found to contain silent mutations, one at codon 23 (GGT-->GGA) and the other at codon 67 (GGC-->GGT). Mutations in the TP53 gene were observed in 46% of the ovarian tumour specimens. We conclude that CDKN2 gene alterations are rare events in human ovarian cancer. The low prevalence of these alterations do not allow for analysis of an association of this gene with prognosis.
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PMID:Sporadic CDKN2 (MTS1/p16ink4) gene alterations in human ovarian tumours. 885 76

Normal ovarian and ovarian cancer tissues from 35 patients were tested for LDH-A-ras protein complex formation, as well as for the expression of ras and LDH-A genes. By immunodetection of the immunoprecipitates, LDH-A-ras protein complexes are present in the homogenates of human ovarian tissues (benign and malignant). Two bands of 21 and 36 kDa were demonstrated in affinity-purified LDH active fractions by Western blot analysis, and these two proteins were proved to be ras p21 and LDH-A by immunodetection. By Northern blot analysis, elevated levels of c-Ki-ras and LDH-A mRNA transcripts were noted in 49% (17/35) and 40% (14/35) of ovarian cancers, respectively. Concurrent high expression of both genes was demonstrated in 11 cases (31%). Tyrosylphosphorylation of LDH-A was demonstrated in normal and malignant ovarian tissues, and the extent of phosphorylation was correlated with the stage of ovarian cancer. The concurrent elevated expression of ras and LDH-A in the same ovarian tissue may imply that the increased synthesis of LDH-A is due to increased or amplified signaling of the ras-cascade pathway. The possible biochemical role of the tyrosylphosphorylated LDH-A complexed with ras p21 in cell transformation and progression of human ovarian cancer is worthy of further investigation.
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PMID:Identification of LDH-ras p21 protein complex and expression of these genes in human ovarian cancer. 899 58


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