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 majority of ovarian cancer patients are treated with platinum-based chemotherapy, but the emergence of resistance to such chemotherapy severely limits its overall effectiveness. We have shown that development of resistance to this treatment can modify cell signaling responses in a model system wherein cisplatin treatment has altered cell responsiveness to ligands of the erbB receptor family. A cisplatin-resistant ovarian carcinoma cell line PE01CDDP was derived from the parent PE01 line by exposure to increasing concentrations of cisplatin, eventually obtaining a 20-fold level of resistance. Whereas PE01 cells were growth stimulated by the erbB receptor-activating ligands, such as transforming growth factor-alpha (TGFalpha), NRG1alpha, and NRG1beta, the PE01CDDP line was growth inhibited by TGFalpha and NRG1beta but unaffected by NRG1alpha. TGFalpha increased apoptosis in PE01CDDP cells but decreased apoptosis in PE01 cells. Differences in extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling were also found, which may be implicated in the altered cell response to ligands. Microarray analysis revealed 51 genes whose mRNA increased by at least 2-fold in PE01CDDP cells relative to PE01 (including FRA1, ETV4, MCM2, AXL, MT3, TRAP1, and FANCG), whereas 36 genes (including IGFBP3, TRAM1, and KRT4 and KRT19) decreased by a similar amount. Differential display reverse transcriptase-PCR identified altered mRNA expression for TCP1, SLP1, proliferating cell nuclear antigen, and ZXDA. Small interfering RNA inhibition of FRA1, TCP1, and MCM2 expression was associated with reduced growth and FRA1 inhibition with enhanced cisplatin sensitivity. Altered expression of these genes by cytotoxic exposure may provide survival advantages to cells including deregulation of signaling pathways, which may be critical in the development of drug resistance.
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PMID:Altered ErbB receptor signaling and gene expression in cisplatin-resistant ovarian cancer. 1606 61

Zinc-finger protein 217 (ZNF217), which is overexpressed during cancer progression, can promote tumor cell immortalization. To examine the function of ZNF217, a global expression profile was carried out using Affymetrix Gene Chip analysis with HG-U133 plus 2.0 arrays in the ovarian cancer cell line HO-8910 after silencing of the ZNF217 gene. The results were analyzed using the Gene Ontology program to investigate the functional network affected by ZNF217 in ovarian cancer cells. Changes in the mRNA expression of the affected genes were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the ZNF217 gene is a key regulator of ovarian cancer, as the silencing of ZNF217 resulted in significant down-regulation by at least 8-fold of 164 genes in the HO-8910 cell line compared to non-silenced control cells. Among these down-regulated genes were ALOX15, CD1D, FXYD3, GAS6, KRT4, LIN7B, MMP-24, PDZK1, PEX6, PRSS8, SLC2A9, STRN and WFDC2. Down-regulation was confirmed by real-time RT-PCR after the silencing of ZNF217 (p<0.05). The results suggest that ZNF217 plays a central role in malignant processes in ovarian cancer.
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PMID:Microarray analysis of gene expression in the ovarian cancer cell line HO-8910 with silencing of the ZNF217 gene. 2147 12