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

The use of medroxyprogesterone acetate (MPA) was incorporated into a nuclear receptor assay for progestin receptor in human endometrium. The assay was developed because MPA is a better ligand than progesterone since it does not bind to corticosteroid-binding globulin and gives greater kinetic stability to the nuclear complex. The MPA nuclear receptor complex for malignant endometrium dissociated at a faster rate than did the complex obtained from normal endometrium, an alteration in binding kinetics which could not be explained by instability of the receptors from malignant endometrium. Factors, including radiation therapy, plasma proteins, endogenous steroids, receptor degradation, tissue heterogeneity, and limited sample size, which influence the interpretation of receptor assay were systematically evaluated. In spite of these controls, it would be premature to conclude that the clinical observations indicate altered receptor from malignant tissue. Further studies are required on endometrial carcinoma which is free of normal tissue fragments. Clinically, nuclear receptor levels were highest in normal endometrium but decreased in samples of malignant endometrium as tumors became more anaplastic. The lowest nuclear binding activity was detected in samples of metastatic endometrial tissue (carcinoma). Hopefully, this nuclear receptor assay (which uses MPA because its dissociation was slower than progesterone) will provide data for correlating clinical response to therapy.
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PMID:Nuclear progestin receptors in normal and malignant human endometrium. 42 86

In our previous paper, it was reported that in human endometrium the step of formation of nuclear receptor-estradiol complex was not temperature-dependent but in rat uteri it was temperature-dependent. In order to clarify whether this temperature dependency in rat uteri means an energy requirement for this step or not, experiments with 2,4-dinitrophenol as an energy uncoupler were done. Even when rat uteri or endometrium of women were incubated with 10 mcc of tritiated-estradiol and 10 (-4) M of 2,4-dinitrophenol, 8S estrogen receptor-estradiol-17beta (E2) complex in cytosol and 5S estrogen receptor-E2 complex in nuclear extract were recognized in both rat and woman. Namely, no evidence was recognized for this step to require activation energy in rat uterus as well as in human endometrium. The cytosol fraction was prepared after human endometrium had been incubated with tritiated-E2 at 2 degrees C. Cytosol was analyzed on sucrose density gradient after heat treatment (at 10 degrees C, 31 degrees C, or 37 degrees C). At 31 degrees C and 37 degrees C treatment, the 8S receptor peak was difficulty recognized. Namely, the 8S receptor-E2 complex was heat labile in cell free condition. This appears to be 1 of the reasons why 8S cytosol receptor was not visible in human endometrium incubated with teritiated-E2 at 37 degrees C. When the cytosol fraction from the human endometrium was analyzed on 3-20% linear sucrose gradient containing .4 M KC1, the peak 8S diminished and about 4S peak appeared. This was considered to mean that 8S receptor in human endometrium was also split to a 4S binding unit at high salt condition and the 8S receptor in humans had also a subunit structure. 8S receptor in cytosol and 5S receptor in nuclear fraction were recognized in 1 case of human endometrial carcinoma, but in another case both receptors were not recognized. Estrogen binding protein in human serum was sedimented at 6S fraction by sucrose gradient.
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PMID:[Estrogen receptor in human endometrium--energy requirement, stability and subunit structure-- (author's transl)]. 103 70

We have studied by immunocytochemistry and monoclonal antibodies the presence and localization of estrogen receptors, progesterone receptors, and a 24-kD estrogen-regulated heat shock protein in biopsies from breast and endometrial cancer patients. Three different tissue processing protocols were used to colocalize the antigens in the same tissue sections: a) frozen sections, b) formalin fixation with routine paraffin embedding, and c) picric acid-formaldehyde (PAF) fixation with a rapid embedding in paraffin. Frozen sections showed good receptor staining but poor 24-kD protein immunoreactivity, while routine paraffin sections (with or without DNase pretreatment) were inadequate to reveal the nuclear receptor proteins at the same level seen in frozen sections. On the other hand, all three proteins could be detected satisfactorily in PAF-fixed paraffin-embedded tissue. Using this procedure we were able to visualize 24-kD protein and estrogen receptor or progesterone receptor in individual cells in paraffin sections. The study revealed that in all of the estrogen receptor positive breast and endometrial tumor samples, almost 90% of the cells expressing the cytoplasmic 24-kD protein contained estrogen receptor in the cell nucleus. In contrast, 24-kD immunoreactive cells did not express progesterone receptors in almost 40% of the progesterone receptor positive tumor samples.
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PMID:Colocalization of estrogen and progesterone receptors with an estrogen-regulated heat shock protein in paraffin sections of human breast and endometrial cancer tissue. 208 75

The Authors studied the concentration of cytosolic and nuclear receptor for Estradiol and Progesterone in endometrial hyperplasia and carcinoma, compared with a control group. Comparative study of hormone receptor concentrations in different populations shows: 1) A significant increase in Estradiol receptors in endometrial hyperplasia (p less than 0.01); 2) A decreasing concentration of estradiol receptors with the decreasing of cellular differentiation in endometrial carcinoma (p less than 0.01); 3) A similar tendency and significance for Progesterone receptors; 4) For both receptors the tendency in the nuclear compartment is similar to that in cytosol but the significance is smaller (p less than 0.05).
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PMID:Hormonal receptors in endometrial neoplasias. 297 93

Both soluble and nuclear oestrogen receptors have been measured in at least two separate sections from 72 endometrial cancers and 12 normal endometria. Concentration of oestrogen receptor is shown to be, in our hands, more meaningful when expressed per unit DNA than per unit protein, whether for soluble or nuclear receptor. Endometrial cancer cells from the central part of the tumour are shown to be receptor negative more frequently than those from peripheral tumour. Thus, in large cancers, biopsies from different areas are required before a tumour can be correctly designated as receptor positive, heterogeneous or receptor negative. The intratumoral variation of receptor status may relate to poor prognosis, since patients with homogeneous receptor-positive disease survive significantly longer than those with tumours showing either heterogeneous distribution of receptor or homogeneous absence of receptor. Intratumoral variation in receptor status is found to be more common in the group of patients who are within 7 years of their menopause, than in older patients.
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PMID:Soluble and nuclear oestrogen receptor status of advanced endometrial cancer in relation to subsequent clinical prognosis. 360 46

Estrogen receptor-like 1a (ESRL1a; same as estrogen receptor-related orphan receptors, ERR1) belongs to a subfamily of the nuclear receptor superfamily. We have previously shown that human ESRL1a modulates estrogen responsiveness of the lactoferrin gene promoter in transiently transfected endometrial carcinoma RL95-2 cells. In this study, we cloned and characterized the human ESRL1 gene. Through the fluorescence in situ hybridization method, the ESRL1 gene was localized to the centromere region of chromosome 11q12. Partial sequencing, restriction mapping, and PCR analysis revealed that the ESRL1 gene consists of seven exons and is approximately 20 kb in length. We found that the smallest exon (exon 3) contains 117 bp and the largest exon (exon 7) has 1032 bp. The smallest intron (intron 5) is only 88 bp long and the largest intron (intron 2) is 8 kb long. All introns have the conserved GT and AG dinucleotides present at the donor and acceptor sites, respectively. Like the estrogen receptor, the highly conserved DNA-binding domain of hESRL1a is encoded by exon 2 and exon 3, and the intron/exon junctions (2 and 3) are well conserved between the two genes. Primer extension analysis revealed multiple transcription initiation start sites in human uterine (HeLa, HEC, and RL95-2) cell lines. However, one major initiation start site was found by RNase protection assay. The hESRL1a mRNA is differentially expressed in various human tissues. The nucleotide sequence adjacent to the transcription start sites of the ESRL1 lacks the typical TATA and CAAT boxes but is GC rich and contains 10 consensus Sp1-binding elements and two E boxes. The region that contains these transcription factor-binding elements showed a high level of promoter activity when transiently transfected into RL95-2 cells.
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PMID:Human estrogen receptor-like 1 (ESRL1) gene: genomic organization, chromosomal localization, and promoter characterization. 928

Estrogen receptor-related orphan receptor alpha 1 is a member of the steroid/thyroid nuclear receptor superfamily. We have previously cloned the human estrogen receptor-related orphan receptor alpha 1 (hERR alpha 1) cDNA and demonstrated that it enhances estrogen responsiveness of the lactoferrin gene promoter in transfected human endometrial carcinoma cells. In the present study, we used the hERR alpha 1 cDNA as a probe and isolated the mouse homologue of ERR alpha 1 from the cDNA libraries of the brain and kidney. Sequence comparison between human and mouse ERR alpha 1 (mERR alpha 1) revealed that the homologies are 89% in nucleotides and 97% in amino acids. By electrophoresis mobility shift assay, we showed that the glutathione S-transferase-mERR alpha 1 fusion protein produced in a bacterial system bound to the human ERR alpha 1 DNA-binding element. Mouse uterine nuclear extract also interacted with this DNA element and produced three complexes in the mobility shift assay, one of which was supershifted by the hERR alpha 1 antiserum. A 2.2 kbp transcript was detected by Northern analysis in all adult mouse tissues tested; however, large variations in the amount of ERR alpha 1 mRNA were found among them. Multiple immunoreactive forms of mouse ERR alpha 1 were detected by Western analysis in non-reproductive tissues, whereas a major 53 kDa protein was found in reproductive tissues such as uterus, cervix and vagina. Diethylstilbestrol (DES) stimulated the expression of ERR alpha 1 mRNA in the uterus of 19-day-old mouse. We showed that DES and estradiol, but not progesterone or dexamethasone, enhanced the level of immunoreactive ERR alpha 1 in the mouse uterus. These results demonstrated that the ERR alpha 1 is an estrogen-responsive gene in the mouse uterus and provides a model system with which to study the biological roles of this nuclear orphan receptor.
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PMID:The mouse estrogen receptor-related orphan receptor alpha 1: molecular cloning and estrogen responsiveness. 946 Jun 51

The nuclear receptor for the female hormone progesterone (PR) is widely expressed in uterine cancer. PR is expressed as two proteins (PRA and PRB) with different functions, and in vitro evidence reveals PRA to inhibit PRB function, so the cellular ratio of PRA:PRB is likely to be an important determinant of progesterone action. The relative expression of PRA and B and their involvement in the pathogenesis of endometrial cancer is not known. The aims of this study were to determine PRA and B expression by dual immunofluorescent histochemistry in endometrial adenocarcinomas compared with expression in normal and hyperplastic glands, and to correlate expression in tumors with clinical features including grade. Significantly lower PR levels were found in tumors compared with normal glands and areas of complex atypical hyperplasia within the same specimen. The normal glands expressed both of the isoforms at similar levels, whereas there was increased predominance of one isoform in hyperplastic areas and in tumors, which suggested that the loss of coordinated expression of PR isoforms was an early event in tumor progression. The majority of tumors [27 (58%) of 46] expressed only one PR isoform, and the proportion expressing either PRA or B was the same [14 (30%) of 46, and 13 (28%) of 46, respectively]. One-half of all tumors ([23 (50%) of 46] expressed either PRA only or a predominance of PRA, and a few tumors [10 (22%) of 46] expressed comparable levels of PRA and B. Similar levels of PRA and B were noted only in FIGO grade 1 tumors, whereas higher grades (2 and 3) were associated with a predominance of one isoform. In summary, expression of only one PR isoform was common in endometrial cancers, which indicates that the decreased PR levels observed in these cancers arise from the loss of one PR isoform. Expression of a single PR isoform was associated with higher clinical grade, which suggests a relationship between the loss of PR isoform expression and features of poorer prognosis. Disruption of relative PR isoform expression was observed in complex atypical hyperplasia, which suggests that early alterations in the ratio of PRA:PRB may precede and/or be implicated in the development of endometrial adenocarcinoma. Alterations in the ratio of PR isoform expression are likely to cause disordered regulation of target genes, resulting in altered progestin action in the uterus, and this may be involved in the pathogenesis of endometrial cancer.
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PMID:Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. 1138 93

The immunoperoxidase stain for estrogen and progesterone receptor content in endometrial adenocarcinoma was correlated with the grade and stage, level of myometrial invasion, age and survival of the patients. Anti-estrogen and anti-progesteone receptor monoclonal antibodies were applied to paraffin-embedded tissue from hysterectomy specimens of 100 patients with adenocarcinoma of the endometrium. In 34 of the cases the receptors were studied in the endometrium adjacent to the tumor and compared to the nuclear receptor content in the carcinoma. There was a high inverse correlation between the estrogen receptor status and the grade of tumor (R = - 0.45, P = 0.006). The estrogen receptor measured in the endometrium near the tumor showed a negative correlation with the grade of the tumor (R = -0.42, P = 0.013). The estrogen, but not the progesterone, receptor content, was positively related to the age of the patient (P < 0.05). No significant correlation of the receptor status with the depth of myometrial invasion was found, despite the obvious interdependence between the grade and myometrial invasion. The progesterone receptor staining index appeared to be a distinct independent prognostic factor in endometrial cancer. The immunohistochemical analysis of the steroid hormone status in endometrial cancer therefore offers an alternative to the quantitative ligand-binding assay.
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PMID:An immunohistochemical study of estrogen and progesterone receptors in adenocarcinoma of the endometrium and in the adjacent mucosa. 1157 89

Progesterone is a critical steroid hormone that controls cell proliferation and differentiation in the female reproductive tract. Progesterone acts through two nuclear receptor isoforms, progesterone receptors A and B (PRA and PRB, respectively), each with unique cellular effects. Loss of PRB has recently been linked to the development of poorly differentiated endometrial tumors, a lethal form of cancer. To study the molecular effects of progesterone, progesterone receptors were introduced into Hec50co endometrial cancer cells by adenoviral vectors encoding either PRA or PRB. Progesterone induced the cyclin-dependent kinase inhibitors p21 and p27, thereby significantly reducing the percentage of proliferating cells. Cancer cell invasion was also markedly inhibited as measured by Matrigel invasion studies. Similarly, a differentiated, secretory phenotype was induced by progesterone in cells expressing PRB. However, replicative senescence was induced by progesterone only in cells expressing PRA. Expression array analysis followed by confirmatory semiquantitative reverse transcription-PCR experiments demonstrated a significant progesterone-dependent inhibition of expression of a cadre of cellular adhesion molecules, including fibronectin, integrin alpha3, integrin beta1, integrin beta3, and cadherin 6. The level of down-regulation of adhesion molecule expression was significantly greater in the presence of the B isoform, demonstrating that progesterone acts principally through B receptors to inhibit cancer cell invasiveness modulated by adhesion molecules.
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PMID:Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. 1183 May 47


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