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

The aim of this study was to overtake the mechanism of the control system in endometrial cancer cell line in vitro. Ishikawa cell (IK cell) and HEC-1 cell (HEC cell) derived from endometrial cancers were cultured with serum free medium (SFM-101). IK cell possessed Estrogen receptor (ER), Progesterone receptor (PR), Epidermal growth factor (EGF) and its receptor (EGFR). HEC cell had PR, EGF, and EGFR, however HEC cell did not keep ER. EGF stimulated the growth of IK cell, but the growth of HEC cell was not stimulated by EGF. S phase cells were increased by EGF in IK cell, but were not increased by EGF in HEC cell. The growth of IK cell was stimulated significantly by EGF and Estradiol-17 beta (E2) +EGF than control. However, E2+EGF did not stimulate the growth of IK cell than EGF significantly. Danazol (D) and D+EGF inhibited the growth of IK cell significantly than control. S phase cells were decreased by the treatment of D and D+EGF. From our results, EGF stimulated the growth of ER positive endometrial cancer cell, but EGF did not stimulate ER negative endometrial cancer cell. E2+EGF and EGF stimulated the growth of IK cell as a same. However, D inhibited the growth of IK cell that was stimulated by EGF.
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PMID:[Cell cycle analysis of endometrial cancer cells in vitro treated with growth factor and steroid hormone]. 130

Three hundred and twenty-seven patients with endometrial carcinoma stage I-II were all followed for at least 5 years. The estradiol receptor concentrations were measured in 298 tumors. In 272 cases the progesterone receptor concentrations were measured as well. Both receptors were significant prognostic factors measured as 5 year survival rate. In a Cox regression test stage, degree of differentiation, myometrial invasion and age remained as independent significant factors. Progesterone receptor concentrations were almost significant in a two-sided test including all degrees of differentiation but were significant (p = 0.04) when only poorly differentiated tumors were included. Thus PgR concentrations were used only on poorly differentiated tumors. The patients could be divided into a high risk group (deep myometrial invasion), an intermediate risk group (poorly differentiated carcinomas without deep myometrial invasion but with a low progesterone receptor concentration) and a low risk group (the remaining) with 5 year survival rated of 61%, 80% and 96% respectively.
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PMID:5-year survival rate in endometrial carcinoma stage I-II related to steroid receptor concentration, degree of differentiation, age and myometrial invasion. 158 May 59

By using ovariectomized nude mice, the hormone reactivity of endometrial carcinoma was evaluated. HEC-88nu cultured cells originated from human endometrial carcinoma were first transplanted to the animal in each experiment. Estrogen receptor (ER) of HEC-88nu reveals positive originally. Hormone pellets containing medroxyprogesterone acetate (MPA) and 17 beta-estradiol (E2) were used. The results were as follows: 1. The proliferation of this tumor was accelerated remarkably by administration of E2 pellet. 2. By administration of MPA pellet, the proliferation was inhibited from the beginning but progressed flatly afterwards maintaining 50% of the control. 3. When MPA was administered upon priming the tumor with E2, the proliferation began to be inhibited after 2 weeks developing 60% of suppression 5 weeks later. 4. Progesterone receptor (PR) of the tumor was induced starting at week 2 when E2 was given and revealed 189 fmol/mgP at week 5. 5. As the morphological changes due to hormone, light eosin-stainability, rarefaction and swelling of the cytoplasms were the common characteristics. 6. It was suggested that both hormonal and pharmacological actions take part in the mechanism of progestin to act on endometrial carcinoma.
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PMID:[Growth regulation of sex steroid hormone in endometrial carcinoma transplanted into nude mice]. 183 53

In summary, endometrial cancer is an estrogen-related neoplasm whose precursor lesion, endometrial hyperplasia, may be successfully treated with progestational agents. Trials of adjunctive progestin therapy have failed to demonstrate benefit, even though the malignancy is sensitive to palliative therapy with progestins as well as tamoxifen. Paradoxically, chronic tamoxifen exposure in postmenopausal women may increase the risk of endometrial cancer, and such women must be followed closely. Progesterone receptor may be measured using competitive binding assays or by immunohistochemical techniques. There is tumor heterogeneity with regard to progesterone receptor. Tissues surrounding the cancer may contain progesterone receptor and produce false-positive results in biochemical assays. Last, the presence of progesterone receptor not only predicts responsiveness to progestational therapy, but also confers a survival advantage in patients with endometrial cancer.
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PMID:Hormonal aspects of endometrial cancer. 210 9

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.
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PMID:Monoclonal antibodies to human progesterone receptor: characterization by biochemical and immunohistochemical techniques. 330 78

A previous study evaluated two types of endometrial carcinoma: one with, the other without, associated adenomatous hyperplasia (Groups 1 and 2, respectively). On the basis of histologic observations, the study concluded that Group 1 tumors were likely to be estrogen-dependent, whereas Group 2 tumors appeared to represent a hormone-independent type of cancer. The authors present quantitative biochemical data to support the proposition that Group 1 tumors are likely to be under the influence of estrogen. Progesterone receptor levels, known to be increased by estradiol, were significantly higher in Group 1 than in Group 2. Analysis of histologic variants revealed that some histologic components, such as mucinous adenocarcinoma, squamous components, and stromal foam cells, predominated in Group 1 and may, therefore, be indicative of estrogen action. Certain histologic features, however, such as papillary carcinoma, clear cells, and anaplastic carcinoma with giant tumor cells, were found exclusively in Group 2, thus suggesting a lack of estrogenic influence. These findings indicate that Group 1 and Group 2 endometrial carcinomas may constitute two different biologic entities and, thus, encourage further basic and clinical research to develop specific therapies for patients diagnosed to have endometrial cancer.
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PMID:Progesterone receptors in two groups of endometrial carcinoma. 394 20

The clinicopathologic associations and effect on prognosis of cytoplasmic steroid receptor content were studied in 168 patients with clinical Stage I and II endometrial carcinoma. Cytoplasmic estrogen receptor status was associated (p less than 0.01) with histologic differentiation, nuclear differentiation, and histologic documentation of extrauterine metastases. Progesterone receptor status was related (p less than 0.05) to histologic differentiation and histologic cell type, and combined estrogen receptor/progesterone receptor status was associated (p less than 0.05) with histologic differentiation, peritoneal cytology, extrauterine metastases, and histologic cell type among the 105 patients who had determination of both estrogen and progesterone receptors. Single-factor analysis revealed significant (p less than 0.05) effects of estrogen receptor status, progesterone receptor status, and estrogen receptor/progesterone receptor status on disease-free survival. All other clinicopathologic features significantly (p less than 0.05) affected prognosis, except for peritoneal cytology. With use of stepwise regression analysis of proportional hazards, estrogen receptor, progesterone receptor, and combined estrogen receptor/progesterone receptor status were significant independent prognostic factors, replacing histologic assessment of glandular or nuclear differentiation in the models. These data suggest that receptor status of primary endometrial carcinomas provides important information relevant to tumor behavior which complements the information provided by conventional clinicopathologic analysis.
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PMID:Influence of cytoplasmic steroid receptor content on prognosis of early stage endometrial carcinoma. 398 57

Estradiol dehydrogenase (E2DH) is a well-known progesterone-dependent enzyme in human endometrium, and its induction has been proposed as a means to test hormonal sensitivity of endometrial carcinoma. While administration of progestins to some patients with endometrial carcinoma resulted in increased endometrial E2DH activity, efforts to induce this enzyme, in vitro, in these tumors have been unsuccessful. The reasons for such failure were investigated in the present study. Progesterone receptor (PR) concentrations and E2DH activities were simultaneously measured in proliferative and malignant endometria under organ culture conditions. Cytoplasmic PR concentrations were determined by Scatchard plot analysis of [3H]progesterone binding in fresh samples and in tissue explants incubated in nutrient medium at 37 degrees in a humidified 5% CO2 atmosphere for various periods of time. Parallel incubations of explants with and without 500 ng medroxyprogesterone acetate per ml were carried out for monitoring E2DH induction. In proliferative endometrium, the progesterone-specific binding sites remained stable during the culture periods, and the E2DH activities were stimulated severalfold by medroxyprogesterone acetate. In contrast, the PR concentrations in carcinoma explants were undetectable after a 24-hr period, and this was associated with a lack of increase in E2DH activity. These findings provide evidence that progestin-induced endometrial E2DH activity is a receptor-mediated phenomenon. In addition, these results demonstrate clearly that the ineffectiveness of progestin to induce E2DH in endometrial cancer specimens, in vitro, is related to the instability of PR under culture conditions. It is suggested that any experiment designed to follow effects of steroids on target tissues must take into account the stability of steroid receptors under in vitro conditions.
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PMID:Failure of progestins to induce estradiol dehydrogenase activity in endometrial carcinoma, in vitro. 694 38

The development and growth of gynecological cancers are related to steroid hormone actions. Alternatively, this prompts us to study biological contribution of sex steroids for invasion and metastasis in gynecological cancers. The first step of metastasis is the detachment of tumor cells. The adherens junction forms a main cell-to-cell junctional complex, mainly consisting of E-cadherin, alpha- and beta-catenins, etc. Estrogen suppressed the expression of their mRNAs, and the adhesive function of cells via adherens junction in endometrial cancer cells. Progestin and danazol reversed the estrogen-induced suppression. Estrogen enhanced invasiveness of endometrial cancer cells though the reconstituted basement membrane and interstitium using the Boyden chamber. Progestin reduced the estrogen-induced invasiveness. The final step of metastasis is tumor-derived neovascularization for growth of metastatic cancer cells. Progestin inhibited basic fibroblast growth factor (FGF) activity, which mainly contribute to tumor-derived neovascularization, regardless of growth-inhibition in some endometrial cancers. Progestin inhibits basic FGF in well-differentiated (WD) endometrial cancer cells, but not in poorly differentiated (PD) endometrial cancer cells. TNP470, a inhibitor of vessel endothelial proliferation, inhibited directly basic FGF in the PD. Therefore, the adequate combination therapy of progestin and TNP470 could efficiently inhibit angiogenic potential of heterologous endometrial cancers. The ratio of estrogen receptor exon 5 splicing variant (ER delta E5) to wild type-ER mRNA expression increased in some metastatic lesions of cancers. The dominant expression of ER delta E5 mRNA might be related to metastatic potential of gynecological cancers. Progesterone receptor from A (PR-A), initiated from in-frame AUG present in the PR from B (PR-B) mRNA, lacks the N-terminal 164 amino acids of PR-B, and acts as a progestin-dependent, trans-dominant repressor of PR-B function and other steroid receptor function. The expression of PR-B mRNA was dominantly expressed in all metastatic gynecological cancers given. This might be related to metastatic potential of gynecological cancers. To know tumorigenic potential of sex steroid receptors, ER, PR-A and PR-B genes were transfected to NIH3T3 cells. Transfected cells with PR-A gene alone formed a few colonies in double soft agar. On the other hand, the cells with PR-B and ER genes under the presence of estradiol formed plenty of colonies. Therefore, overexpression of PR-B under the absence of PR-A might be related to tumorigenic potential. In conclusion, estrogen could enhance some steps of metastasis in endometrial cancers, and progestin could inhibit the estrogen-induced events, regardless of growth-inhibition. Relative over-expression of ER exon 5 splicing variant, and PR-B might contribute to metastatic potential in gynecological cancers.
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PMID:[Endocrinological contribution for invasion and metastasis in gynecological cancers]. 880 31

A methanol extract of chaste-tree berry (Vitex agnus-castus L.) was tested for its ability to displace radiolabeled estradiol from the binding site of estrogen receptors alpha (ERalpha) and beta (ERbeta). The extract at 46 +/- 3 microg/ml displaced 50% of estradiol from ERalpha and 64 +/- 4 microg/ml from ERbeta. Treatment of the ER+ hormone-dependent T47D:A18 breast cancer cell line with the extract induced up-regulation of ERbeta mRNA. Progesterone receptor (PR) mRNA was upregulated in the Ishikawa endometrial cancer cell line. However, chaste-tree berry extract did not induce estrogen-dependent alkaline phosphatase (AP) activity in Ishikawa cells. Bioassay-guided isolation, utilizing ER binding as a monitor, resulted in the isolation of linoleic acid as one possible estrogenic component of the extract. The use of pulsed ultrafiltration liquid chromatography-mass spectrometry, which is an affinity-based screening technique, also identified linoleic acid as an ER ligand based on its selective affinity, molecular weight, and retention time. Linoleic acid also stimulated mRNA ERbeta expression in T47D:A18 cells, PR expression in Ishikawa cells, but not AP activity in Ishikawa cells. These data suggest that linoleic acid from the fruits of Vitex agnus-castus can bind to estrogen receptors and induce certain estrogen inducible genes.
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PMID:Isolation of linoleic acid as an estrogenic compound from the fruits of Vitex agnus-castus L. (chaste-berry). 1497 42


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