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

A protein factor which stimulated [3H]thymidine uptake into free hepatocytes prepared from normal mouse liver was detected in the ascitic fluid of gynecological cancer patients. The factor was subsequently further purified from the ascitic fluid of an endometrial cancer patient by DEAE-Sephacel, Sephadex G-150 and Phenyl-Sepharose CL-4B column chromatographies, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a single protein band of 54,000 Da, designated tentatively as 54K ascitic protein (54K-AP). 54K-AP was similar to human alpha 1-antitrypsin (alpha 1-AT) in terms of SDS-PAGE and immunological behavior, but was slightly different in terms of amino acid sequence and isoelectric point. Although 54K-AP inhibited the activities of bovine trypsin and alpha-chymotrypsin as did human alpha 1-AT, 54K-AP inhibited the plasminogen activator released from human endometrial cancer Ishikawa cells more efficiently than alpha 1-AT. Because, in contrast to normal serum, the serum from the endometrial cancer patients stimulated [3H]thymidine uptake into hepatocytes, the possibility arises that 54K-AP could be produced by the cancer host as a defence mechanism against the cancer.
 ...
PMID:Characterization of a 54 kDa, alpha 1-antitrypsin-like protein isolated from ascitic fluid of an endometrial cancer patient. 190 55

Progesterone receptor (PR) from a human endometrial carcinoma (EnCa 101) grown in nude mice consists of two hormone-binding proteins with mol wt around 116,000 and 85,000. To generate monoclonal antibodies against this receptor, PR was partially purified from EnCa 101 and used to immunize Robertsonian mice. Immune mouse spleens were fused with HL-1 Friendly myeloma-653 cells, and hybridomas were screened by solid phase dot-blot assay and double antibody precipitation. Seven stable hybridomas were obtained, designated hPRa 1-7. Subisotyping revealed that hPRa 1 and 6 were immunoglobulin G2b, while the remainder were immunoglobulin G1. Ultracentrifugation in high salt sucrose gradients showed that six of the seven antibodies effected a shift of [3H]progestin-labeled PR from EnCa 101; only hPRa 4 was ineffective in this regard. Protein blots of EnCa 101 cytosols and DEAE eluates revealed that hPRa 1, 3, 4, 5, and 7 recognized both PR proteins equally. hPRa 2 recognized principally the 116,000 mol wt PR protein; it recognized the lower mol wt PR protein very poorly if at all, whereas hPRa 6 recognized only the 116,000 mol wt protein. Interestingly, the latter was consistently detected as a closely migrating triplet. Immunolocalization of PR by hPRa 1-7 in tissue sections was confined to nuclei of target tissues and varied in intensity: hPRa 7 greater than 3 = 5 greater than 6 = 2 greater than 1 greater than 4. In proliferative phase uterus, the intensity of staining was ranked: endometrial gland nuclei (3+) greater than myometrial cell nuclei (2-3+) greater than endometrial stromal cell nuclei (0-1+). Thus, seven monoclonal antibodies directed against human PR have been prepared, and their suitability for the study of PR by biochemical and immunohistochemical techniques has been demonstrated.
 ...
PMID:Monoclonal antibodies to human progesterone receptor: characterization by biochemical and immunohistochemical techniques. 330 78

A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed, from 130 +/- 55 (SD) fmol/mg protein to 1,311 +/- 598 fmol/mg protein and 710 +/- 310 fmol/mg protein, respectively. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with [17 alpha-methyl-3H]promegestone ([3H]R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Coomassie blue staining of gels revealed that the protein patterns of all of the partially purified preparations from EnCa 101, EnCa K, and EnCa V were essentially identical. In contrast, photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of [3H]R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. In each case, the labeling was competable with excess non-radioactive R5020. No incorporation of [3H]R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.
 ...
PMID:Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma. 405 15

In medical clinics or experiments, progesterone (P) has been used for treatment of adenomatous hyperplasia or cancer of the endometrium. In the present paper, effects of P in combination with or without estradiol-17 beta (E2) on the estrogen receptor (ER) and thymidine kinase (TK) activity in immature rat uterus are described. P has been reported to interfere with the replenishment of the cytoplasmic ER of the rat uterus. In the present study, no translocation of the cytoplasmic ER to the nucleus was found after the injection of P, whereas P slightly enhanced the wet weight and the TK activity of the uterus. The TK activity increased 20 to 30 times the control level at 30 hours after the injection of E2. However, the enzyme activity induced by E2 was inhibited by P which was approximately 1,000-fold or more dose of E2. This enzyme was separated into isozymes by DEAE-cellulose column chromatography. Induction of the specific TK isozyme, which was induced by E2 in immature rat uterus and closely related to DNA synthesis, was found to be inhibited by P.
 ...
PMID:[Estrogen and progesterone interactions on the estrogen receptor and thymidine kinase in the immature rat uterus]. 715 94

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.
 ...
PMID:Epidermal growth factor activates protein kinase C in the human endometrial cancer cell line HEC-1-A. 934 55