Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bradykinin may act as a promoter of endometrial regeneration. In [3H]myristate-labelled endometrial stromal cells, bradykinin and tetradecanoylphorbol acetate (TPA) mediated activation of phospholipase D (PLD) as measured by the accumulation of [3H]phosphatidylbutanol ([3H]PtdBut). Kinetics of bradykinin-evoked PLD activation was rapid and transient, whereas the TPA response was relatively slow in onset. Bradykinin induced a dose-dependent (EC50 0.11 nM) [3H]PtdBut accumulation at concentrations at which it stimulated DNA synthesis. In [3H]inositol-labelled cells, bradykinin evoked a rapid increase in inositol phosphates which preceded the increase in [3H]PtdBut formation. Chronic pretreatment with 400 nM TPA abolished PLD activation to subsequent treatment with either TPA and bradykinin. Staurosporine, an inhibitor of protein kinase C, strongly inhibited (IC50 96 nM) TPA-induced [3H]PtdBut formation, but bradykinin-stimulated [3H]PtdBut accumulation was only partially inhibited (IC50 65 microM). The effect of bradykinin and TPA on PLD activity was synergistic, suggesting that the two agents may act via different mechanisms. These results suggest PKC-dependent and independent pathways are involved in bradykinin-induced PLD activation and that the mitogenic activity of this vasoactive peptide on endometrial stromal cells may in part be mediated via the PLD pathway. This may have significance both to implantation and endometrial cancer.
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PMID:Activation of human endometrial phospholipase D by bradykinin. 858 76

In single endometrial carcinoma HEC-1A and Ishikawa cells, ATP induced a rapid and extracellular Ca2+-independent rise in cytosolic Ca2+ concentration ([Ca2+]i) in a dose-dependent manner, with an ED50 of about 10 microM. The spike phase was followed by a sustained plateau phase that was dependent on Ca2+ influx through voltage-insensitive Ca2+ channels, whose gating was controlled by a capacitative Ca2+ entry mechanism. ADP was less potent in raising the cystolic Ca2+ concentration, and AMP and adenosine were ineffective. The order of agonist potency for this receptor was ATP = UTP > ATP-gamma-S >> ADP. Several other agonists, including beta,gamma-methylene-ATP, 2-MeS-ATP, and BzATP were ineffective. This ligand-selective profile indicates the expression of the P2Y2R subtype in endometrial cells. Accordingly, reverse transcription-PCR using P2Y2 primers amplified the expected transcript from both cell lines. The coupling of these receptors to phospholipase C was confirmed by the ability of ATP to increase inositol 1,4,5-trisphosphate and diacylglycerol productions. These receptors are also coupled to the phospholipase D-1 pathway, leading to accumulation of phosphatidic acid. Activation of P2Y2 receptors by a slowly degradable ATP analog, ATP-gamma-S, was associated with a significant suppression of cell proliferation without affecting the cellular apoptosis. These results indicate that P2Y2 receptors may participate in control of the cell cycle of endometrial carcinoma cells.
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PMID:Expression and responsiveness of P2Y2 receptors in human endometrial cancer cell lines. 1056 54

Background: The concentrations of three N-acylethanolamines (NAEs), anandamide (AEA), N-oleoylethanolamide (OEA), and N-palmitylethanolamide (PEA) are increased in the endometria of women with endometrial cancer (EC). It is widely accepted that plasma levels of these three NAEs are regulated by the actions of the rate-limiting enzymes N-acylphoshatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), which are synthesizing and degradative, respectively. The expression and activity of these enzymes have not previously been studied in EC. Methods: FAAH activity in peripheral blood lymphocytes, and transcript and protein expression for FAAH and NAPE-PLD in EC tissues were measured using enzyme, quantitative RT-PCR, and histomorphometry (of immunoreactive tissue sections), respectively. Samples were from 6 post-menopausal women with atrophic endometria (controls) and 34 women with histologically diagnosed EC. Concentrations of the three NAEs also measured in plasma and tissues were correlated with lymphocytic FAAH activity and the NAPE-PLD and FAAH transcript and protein levels. Results: Peripheral lymphocyte FAAH activity was unaffected in women with EC compared to controls. The FAAH transcript expression level was significantly (p < 0.0001) 75% lower in EC whilst NAPE-PLD levels were not significantly (p = 0.798) increased. In line with the transcript data, a significant (p < 0.0001) tumor type-dependent 70-90% decrease in FAAH protein and significant 4- to 14-fold increase in NAPE-PLD protein (p < 0.0001) was observed in the malignant tissue with more advanced disease having lower FAAH and higher NAPE-PLD expression than less advanced disease. Correlation analyses also confirmed that tissue NAE concentrations were inversely related to FAAH expression and directly correlated to NAPE-PLD expression and the NAPE-PLD/FAAH ratio. Conclusion: These data support our previous observation of tissue levels of AEA, OEA, and PEA and a role for NAE metabolism in the pathogenesis of EC.
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PMID:Expression and Function of the Endocannabinoid Modulating Enzymes Fatty Acid Amide Hydrolase and N-Acylphosphatidylethanolamine-Specific Phospholipase D in Endometrial Carcinoma. 3192 30