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

Staurosporine is a potent apoptosis inducer, but its mechanism remains to be clarified. We investigated the involvement of PTEN in staurosporine-induced apoptosis. Ishikawa cells, from an endometrial carcinoma cell line, expressed a high amount of PTEN mRNA but did not express the PTEN protein because of protein truncations. We isolated clones expressing the steady-state level of the PTEN protein from PTEN-null Ishikawa cells by transfection. The obtained clones showed reduced proliferative activity and reduced anchorage-independent cell growth with the augmented p27(Kip1). These cell lines were sensitized to apoptosis by staurosporine. A low concentration of UCN-01 did not affect apoptosis, but a high concentration augmented apoptosis in the PTEN-expressing clone. Alpha-sphingosine and H-7 did not affect apoptosis in these cell lines. PI3K inhibition augmented staurosporine-induced apoptosis in the parental cell line, but not in the PTEN-expressing clone. In the clone, phosho-Akt/PKB and phospho-Bad (Ser-136) were downregulated. Staurosporine reduced the levels of phospho-Akt/PKB and phospho-Bad (Ser-136) in all the cell lines, but the reduction was most significant in the PTEN-expressing clone. These results suggest that inhibition of the PI3K/Akt/PKB signaling pathway might be associated with staurosporine-induced apoptosis in Ishikawa cells.
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PMID:PTEN augments staurosporine-induced apoptosis in PTEN-null Ishikawa cells by downregulating PI3K/Akt signaling pathway. 1196 94