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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand how type I and II endometrial tumors uniquely respond to tyrosine kinase inhibitor treatments, we evaluated the signaling pathways of epidermal growth factor (EGF) receptor (EGFR) under the effects of EGF and Iressa (ZD1839, gefitinib) using Ishikawa H and Hec50co cells that model type I and II endometrial carcinomas, respectively. The cells were assayed for the expression of EGFR and both cell lines express an average of 100,000 EGFR per cell; however, Ishikawa H cells express higher levels of HER-2/neu compared with Hec50co cells (1.38 x 10(5) compared with 2.04 x 10(4), respectively). Using the Kinetworks multi-immunoblotting approach, which profiles 31 signaling phosphoproteins, the most striking result was that Hec50co cells show a higher number of basal phosphorylated sites compared with Ishikawa H cells. Furthermore, we identified targets of Iressa treatment in both cell lines. Iressa, at a dose of 1 micromol/L, blocked the autophosphorylation of EGFR in Ishikawa H and Hec50co cells with some distinctive effects on downstream effectors. Nevertheless, in both cell lines, EGF stimulated and Iressa blocked the major EGFR target mitogen-activated protein kinases extracellular signal-regulated kinase 1 and 2 equally. The high basal phosphorylation of numerous signaling molecules in Hec50co cells that were not inhibited by Iressa indicates that other growth factor pathways are active in addition to EGFR. We conclude that endometrial cancer cells that model type I and II carcinomas have the capacity to respond to EGFR inhibition as a therapeutic strategy; however, the response of the more aggressive type II tumors may be limited by the constitutive activation of other signaling pathways.
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PMID:Regulation of signaling phosphoproteins by epidermal growth factor and Iressa (ZD1839) in human endometrial cancer cells that model type I and II tumors. 1637 4

In this study, we investigated if Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, augments endometrial cancer (EC) therapy with medroxyprogesterone acetate (MPA). Combined treatment with Gefitinib plus MPA decreased the proliferation and invasiveness of the Ishikawa and RL952 EC cell lines more effectively than MPA treatment alone. Moreover, combined treatment with Gefitinib plus MPA reduced growth of EC xenografts in Balb/c nude mice more than either Gefitinib or MPA alone. The therapeutic efficacy of combined Gefitinib plus MPA treatment was dependent on expression of dual-specificity phosphatase 1 (DUSP1). DUSP1 knockdown in Ishikawa cells treated with Gefitinib plus MPA showed greater proliferation and invasiveness than parental Ishikawa cells treated similarly. EC cells treated with the combination of Gefitinib plus MPA also showed DUSP1-dependent reductions in phospho-ERK1/2 and increases in E-Cadherin. Thus, Gefitinib appears to DUSP1-dependently enhance the therapeutic efficacy of progestin in EC cells.
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PMID:Gefitinib enhances sensitivity of endometrial cancer cells to progestin therapy via dual-specificity phosphatase 1. 2938 65