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

Under the previous data of the presence of fos/jun expression via protein kinase C (PKC) activation by estrogen in endometrial cancer cell line (1), the following experiment was made on the endometrial cancer tissue of the human subject. The ratio of membrane/cytosol PKC activity and the level of fos/jun expression were significantly higher in well differentiated endometrial cancers than in those of moderately or poorly differentiated ones. Those two in the endometrial cancer were significantly higher than those in the normal counterpart. The ratio and the expression in normal uterine endometria of the proliferative phase were significantly higher than those in the secretory phase. Both in the endometria were significantly enhanced 1 week after the administration of estrogen. It is suggested that the linkage of fos/jun expression via PKC activation by estrogen might be exaggerated in the endometrial cancers, especially in the well differentiated, plausibly with the loss of the anti-estrogen effect of progesterone, but dedifferentiation might lose this linkage.
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PMID:Clinical implication of fos and jun expressions and protein kinase activity in endometrial cancers. 764 41

Calphobindin I (CPB I) is a member of the family of Ca(2+)-dependent phospholipid binding proteins collectively termed as annexins. CPB I (Annexin V) has recently been shown to be an endogenous inhibitor of protein kinase C, a key enzyme in the cellular signal transduction and its inhibition by CPB I is presumed to be related ultimately to carcinogenesis. We therefore examined the level of production of CPB I in uterine cancer cells. Immunohistochemical analysis, northern blot, and in situ hybridization showed that the production of CPB I was markedly suppressed at the level of transcription in both cervical and endometrial carcinoma cells when compared to their normal counterparts. Decrease in production of CPB I may lead to dysregulated activation of protein kinase C and, accordingly, may be involved in a disorder of cell differentiation, proliferation, and carcinogenesis.
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PMID:Suppression of calphobindin I (CPB I) production in carcinoma of uterine cervix and endometrium. 767 95

The present study was undertaken to determine whether endometrial cancer cell line HEC-1-A differ from nontransformed cells, in that the cAMP and protein kinase C pathways may enhance IGF-I effects in mitogenesis by acting at the G1 phase of the cell cycle instead of G0. Immunofluorescence staining of HEC-1-A cells using the proliferating cell nuclear antigen (PCNA) monoclonal antibody and flow cytometric analysis determined that HEC-1-A cells do not enter the G0 phase of the cell cycle when incubated in a serum-free medium. Approximately 51% of the cells were in G1, 12% were in S and 37% in G2 phase of the cell cycle prior to treatment. Forskolin and phorbol-12-myristate 13-acetate (PMA) were used to stimulate cAMP production and protein kinase C activity, respectively. IGF-I, forskolin and PMA each increased (P < 0.01) [3H]-thymidine incorporation in a dose and time dependent manner. The interaction of forskolin and PMA with IGF-I was then determined. Cells preincubated with forskolin or PMA followed by incubation with IFG-I incorporated significantly more (P < 0.01) [3H]-thymidine into DNA than controls or any treatment alone. It is concluded that forskolin and, to a lesser extent, PMA exert their effect at the G1 phase of the cycle to enhance IGF-I effects in cell proliferation.
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PMID:cAMP and PMA enhance the effects of IGF-I in the proliferation of endometrial adenocarcinoma cell line HEC-1-A by acting at the G1 phase of the cell cycle. 773 22

A plasminogen activator (PA) system is involved in ovulation, implantation, tumor invasion and metastasis. In order to clarify the regulation of this PA system in endometrial cells, we examined which agent affecting cellular function altered tissue-type plasminogen activator (t-PA) secretion by endometrial carcinoma cell line (KLE cells) in vitro. Triiodothyronine, retinoic acid, insulin, 8-bromo-cAMP, PDGF, IGF-I, basic FGF or TNF-alpha did not alter t-PA secretion while the activator of protein kinase C, phorbol myristate acetate (PMA) stimulated t-PA secretion in a dose-dependent fashion (10(-10)-10(-8) M). The time required to give a statistically significant increase in t-PA over control was 3 hours, and the maximal increase was seen after 24 hours of exposure. Another active phorbol ester, PDD also stimulated t-PA secretion while inactive forms of phorbol ester, 4 alpha-PDD and phorbol did not alter it. Cholera toxin or 8-bromo-cAMP did not affect t-PA secretion, but enhanced PMA-stimulated t-PA secretion. Cycloheximide and actinomycin D completely abolished PMA-stimulated t-PA secretion. These results suggest that (1) t-PA secretion in the endometrial carcinoma cell is modulated by a protein kinase C system, (2) This effect is through new RNA production and protein synthesis. (3) There is a complicated relationship between protein the kinase C and protein kinase A system as to the regulation of t-PA secretion. This would be a suitable model to clarify the PA system in endometrial cells.
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PMID:[Effect of phorbol ester on tissue-type plasminogen activator (t-PA) secretion in endometrial carcinoma cell line in vitro]. 812 84

To study the early effects of steroid hormones on cells we investigated the influence of the sex steroids and tamoxifen on phospholipid turnover in endometrial carcinoma and breast cancer cells. Studies were performed on 19 human uterine adenocarcinomas and 29 breast cancer tumors. Progesterone in a final concentration of 10(-7) mol/l caused a twofold decrease of 32P incorporation into phospholipids (phosphatidylcholine and phosphoinositides) in 85% of the uterine adenocarcinomas where the progesterone receptor (PR) content was more than 100 nmol/kg and only in 30% of the tumors where the PR content was less than 100 nmol/kg. Treatment of the cells with 10(-8) mol/l 17 beta-estradiol or 10(-8) mol/l epidermal growth factor led to an increase in 32P incorporation into phospholipids. Analysis of the hormonal responsiveness of 29 human breast cancers showed that 17 beta-estradiol increased 32P incorporation into phospholipids in 47% of the tumors where the estradiol receptor (ER) content was more than 10 nmol/kg and in 21% of the receptor-negative tumors (ER < 10 nmol/kg) The results show that phospholipid turnover in uterine and breast cells can be regulated by sex steroids. Treatment of the breast cancer cells with the antiestrogen tamoxifen (10(-6) mol/l) led to an increase of 32P incorporation into phosphoinositides and a decrease of 32P incorporation into phosphatidylcholine. Addition of an activator of protein kinase C, i.e. 2 x 10(-7) mol/l 12-0-tetradecanoylphorbol-13-acetate, weakened the inhibitory effect of tamoxifen on phosphatidylcholine turnover. These findings suggest that tamoxifen action can be mediated via an alteration of the growth signal transducing system.
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PMID:Regulation of phospholipid turnover by steroid hormones in endometrial carcinoma and breast cancer cells. 839 60

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

Endometrial fibroblasts derived from uterine endometrium as controls and endometrial cancer cell lines (Ishikawa and HHUA cells) were analyzed for the induction manner of c-fos and c-jun transcripts in endometrial cancers, some of which are estrogen-dependent in growth. Estrogen increased c-fos expression and protein kinase C (PKC) activity in fibroblasts and Ishikawa cells, but not in HHUA cells. Progesterone diminished c-fos and c-jun expression and PKC activity induced by estradiol in the fibroblasts, but not in Ishikawa cells, which persistently overexpressed c-fos and c-jun. In these cells, 12-0-tetra-decanoylphorbol-13-acetate (TPA) increased c-fos and c-jun expression as did estradiol. Pretreatment with 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) abolished estrogen-inducible over-expression of c-fos and c-jun. The combination of both estradiol and TPA at maximum effective concentration exerted no additive and synergistic effect on induction of c-fos and c-jun expression. In conclusion, persistent activation of PKC might lead to overexpression of c-fos and c-jun in some endometrial cancers with an estrogen predominant milieu, which might be, at least in part, associated with the transformation or growth potential.
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PMID:Estrogen induces expression of c-fos and c-jun via activation of protein kinase C in an endometrial cancer cell line and fibroblasts derived from human uterine endometrium. 870 84

Tamoxifen has been used most commonly to treat breast and endometrial cancer, two malignancies in which the antiestrogenic properties of tamoxifen have substantial therapeutic benefit. However, tamoxifen has been used in the treatment of other cancers as well, some in which an antiestrogen may be effective, but others in which estrogen receptor is not expressed. In estrogen receptor-negative cancers, tamoxifen has been shown to have therapeutic activity at doses approximately fourfold to eightfold above those used for estrogen receptor inhibition. It is thought that the primary mechanism of tamoxifen in estrogen-negative tumors is inhibition of protein kinase C. Clinical trials of tamoxifen in ovarian cancer, hepatocellular carcinoma, desmoid tumors, malignant glioma, pancreatic carcinoma, melanoma, and renal cell carcinoma are reviewed.
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PMID:Tamoxifen for the treatment of malignancies other than breast and endometrial carcinoma. 904 18

We studied the involvement of annexin V in the antiproliferative effects of gonadotropin-releasing hormone (GnRH) agonists on human endometrial cancer cell line HHUA. HHUA cell line expressed mRNA for GnRH receptors as assessed by reverse transcriptase-PCR with oligonucleotide primers. In the presence of buserelin, the proliferation of this cell line was significantly (P < 0.01) reduced to 60% of control after 72 hr. Peak intracellular concentrations of annexin V, equivalent to about twice the control value, were obtained after 48 hr exposure to buserelin. Intracellular annexin V concentration was increased not only by buserelin, but also by protein kinase C (PKC) activator. However, there was no increase in intracellular annexin V concentration when cells were incubated with PKC inhibitor before the addition of buserelin. The results suggest that GnRH agonists inhibit cell proliferation by increasing intracellular concentrations of annexin V, an effect mediated by the activation of PKC.
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PMID:Involvement of annexin V in antiproliferative effects of gonadotropin-releasing hormone agonists on human endometrial cancer cell line. 926 65

Previous studies from this laboratory have shown that epidermal growth factor (EGF) and the tumor promoter, phorbol myristate acetate (PMA), are mitogenic in the endometrial cancer cell line HEC-1-A. Since the effects of EGF have been shown to be mediated by the protein kinase C (PKC) pathway transduction system, we examined the possibility that the EGF-responsive signal in the endometrial cancer cell line HEC-1-A involves protein kinase C activation. HEC-1-A cells were grown to confluency in 100-mm dishes and maintained in a serum-free medium for 24 hr prior to treatment. The cells were treated with EGF at varying time intervals (0.25 to 60 min) and concentrations (0.1 to 200 ng/ml). The cells were then lysed, homogenized, and centrifuged at 105,000g for 1 hr at 4 degrees C. The supernatant was chromatographed on DEAE-Sephacel columns. The membranous pellet was resuspended in 5 ml of lysis buffer containing 1% Nonidet P-40 and also chromatographed on DEAE-Sephacel columns separately. The eluates were collected and assayed for protein kinase C activity by determining the amount of 32P transferred from [gamma-32P]ATP onto histones in the presence of the phospholipids, phosphatidylserine, and diolein. Our results show that the cytoplasmic and membrane fraction of the HEC-1-A cell line contained phosphotransferase activity which displayed kinetic characteristics typical of the protein kinase C enzyme. The optimal incubation time for protein kinase C activation in the cytosol by EGF was 5 min (30-fold stimulation). The protein kinase C activity was increased when the cell lines were incubated with increasing concentrations of EGF. Enzyme saturation was seen at a concentration of 10 ng/ml of EGF (4.5-fold stimulation). Western blot analysis confirmed the presence of the PKC enzyme in the cytosol and membranes of our cancer cell line. These results suggest that EGF, at least partially, exerts its effects on the endometrial adenocarcinoma cell line by activating protein kinase C through increased breakdown of phosphatidyl inositol (PI). The PI cascade appears to be an important signal transduction system mediating the growth stimulatory effects of EGF on endometrial carcinoma.
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PMID:Epidermal growth factor activates protein kinase C in the human endometrial cancer cell line HEC-1-A. 934 55


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