UMLS:C0476089 - FACTA Search

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

An estrogen (E) independent sub-clone (EIIL) was separated from a human endometrial carcinoma cell line, Ishikawa, by culturing the wild type under an E free condition for 350 days. The cells were then implanted into nude mice subcutaneously and tumors allowed to develop for 35 days. The primary lesions were then excised to stimulate recurrence. One animal developed recurrence with multiple distant metastases. The primary tumor and metastatic tumors from the animal were studied for ErbB-2 expression by immunohystochemical techniques or by a reverse transcription followed by polymerase chain reaction (RT-PCR). Expressions of epidermal growth factor (EGF) receptors, aromatase, nidogen, E receptors, hepatocyte growth factors (HGF) and beta-actin were also examined. The results showed that metastatic lesions expressed high levels of ErbB-2, nidogen and aromatase but unchanged levels of EGF receptors and HGF. The metastatic lesions expressed one third of the E receptors which were detected in the EIIL in vitro. These observations suggest that a decrease in ER along with increased expression of nidogen and aromatase is associated with the process of metastasis and the model appears to be of value in studying the process of the acquisition of a metastatic phenotype.
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PMID:[Establishment of metastatic sub-clone from estrogen independent Ishikawa cells and its characterization in vitro and in vivo]. 769 85

This paper reviews basic and clinical aspects of human prostate cancer, with special regard to steroid hormones and growth factors, their receptors and the use of these tools in clinical practice. Unlike other endocrine-related tumours, such as breast and endometrial cancer, human prostatic carcinoma has distinctive features that crucially hinder its definition in terms of both biological potential and clinical course. Failure of androgen receptors to represent helpful discriminants for both prognosis and treatment of prostate cancer patients may depend upon methodological pitfalls and/or the heterogeneous composition of most tumour tissues. The former involve either technical problems (tissue sampling and storage, assay procedures) or biochemical and biological points (heterogeneity and functional integrity of steroid binding sites, subcellular and tissue distribution of steroid receptors). The latter mostly concern the unique feature of both normal and diseased prostate gland to present regional diversities in hormone sensitivity and steroid receptor content. Another important area of interest resides in the potential role played by stromal-epithelial interaction in the regulation of growth and function of prostate epithelial cells. In this respect, continued growth of androgen-dependent prostate cancer cells is achieved through intricate pathways where mesenchymal steroid-induced polypeptide growth factors may act in a paracrine/autocrine fashion to mediate androgen action on tumor epithelial cells. In particular, epidermal growth factor (EGF) and transforming growth factor-a (TGFa) may serve as androgen intermediaries in the proliferative control of prostate epithelial cells, but may also be involved in androgen-independent autocrine epithelial cell growth. Clinical correlations of androgen receptors in human prostatic carcinoma have been insofal disappointing. Biochemical or histochemical assays have failed to satisfactorily predict prognosis and response to endocrine therapies of patients. This recalls problems in both methodologies and tissue suitability and points to the need of prolonged follow-up studies wherein special care is placed in sampling conditions, identification of high-affinity sites of steroid binding and selection of threshold values for receptor concentrations. Assay of the EGF receptors might provide additional contribution for a deeper inspection of the biological nature of prostate tumour tissues and help in selecting more appropriate individual-based therapeutic strategies.
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PMID:Steroid receptors in prostate cancer tissues and cells: pathophysiology, problems in methodology, clinical value and controversial questions. 800 81

There is compelling evidence that growth factors are involved in mediating estrogen action in target tissues. The role of growth factors in the development and progression of endometrial cancer is less clear. Steroid hormones can regulate the expression of the transforming growth factors and epidermal growth factor receptors in endometrial cancer cells in culture. It is also possible to demonstrate that these growth factors function in an autocrine fashion to regulate proliferation of endometrial cancer cells in culture. Constitutive expression or overexpression of such autocrine/paracrine factors and/or their receptors may be important in the growth progression of endometrial neoplasia. However, to date the evidence to support the hypothesis is limited.
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PMID:Growth factors and steroid hormone action in endometrial cancer. 818 Jan 2

In MCF7 human breast cancer cells, the antiestrogens 4-hydroxy-tamoxifen and ICI 164,384 inhibit the mitogenic activity of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I). These growth factors also stimulate the expression of cathepsin-D and pS2 genes. Therefore, we studied the effects of antiestrogens on growth factor induction of pS2 and cathepsin-D mRNA. The two antiestrogens strongly inhibited the transcriptional induction of pS2 by growth factors. On the contrary, estradiol and IGF-I or EGF had an additive effect on pS2 mRNA accumulation. Growth factor induction of cathepsin-D was also inhibited by ICI 164,384. By contrast, 4-hydroxytamoxifen had an agonist effect on cathepsin-D and an additive effect on IGF-I-induced mRNA. When 12-O-tetradecanoylphorbol-13-acetate or 8-bromo-cAMP (8-Br-cAMP) was used instead of growth factors, similar effects of 4-hydroxytamoxifen and ICI 164,384 were obtained on pS2 (12-O-tetradecanoylphorbol-13-acetate and 8-Br-cAMP) and cathepsin-D (8-Br-cAMP) induction. A mechanism based on the classical competitive inhibition by antiestrogens of estrogen binding and action on the estrogen receptor was very unlikely, as 1) no antigrowth factor activity was obtained with R5020, which was a potent inhibitor of estrogen induction of pS2 and cathepsin-D mRNA; 2) in the Ishikawa endometrial cancer cell line, the cathepsin-D gene is unresponsive to estrogen, but was inhibited by antiestrogen after its induction by EGF or 8-Br-cAMP; and 3) the residual estrogen concentration in cells was too low to induce the expression of estrogen-specific genes. However, antiestrogens did not inhibit the expression of all genes induced by growth factors, as they were without effect on IGF-I induction of glyceraldehyde-3-phosphate dehydrogenase mRNA. These results demonstrate that antiestrogens can modulate the transcription of some growth factor-induced genes and strongly suggest that this effect is not due to interference with residual estrogens.
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PMID:Synthetic antiestrogens modulate induction of pS2 and cathepsin-D messenger ribonucleic acid by growth factors and adenosine 3',5'-monophosphate in MCF7 cells. 834 99

Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent at the cell membranes, with a varying pattern in individual carcinomas. EGF-R expression was not correlated with histologic grade, surgical stage, or estrogen/progesterone receptor status evaluated immunohistochemically or biochemically in adjacent tissue sections of the tumor. Ten of 13 (77%) atrophic/inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas.
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PMID:Expression of epidermal growth factor receptors in human endometrial carcinoma. 834 61

Transforming growth factor-beta 1 (TGF-beta 1) enhanced cell proliferation in a concentration-dependent manner in a human endometrial cancer cell line, IK-90. Scatchard analysis of TGF-beta 1 receptor in IK-90 cells, using 125I-TGF-beta 1 as a ligand, revealed the presence of a class of high-affinity TGF-beta 1 receptors (2,000 sites per cell, KD = 74pM). Moreover, IK-90 cells produced and secreted TGF-beta 1: TGF-beta 1 messenger RNA was detected at 2.5 and 4.0 kb by Northern-blot analysis using 32P-labeled TGF-beta 1 cDNA as a probe, and TGF-beta 1 activity in conditioned medium by the inhibition of 3H-thymidine uptake into CCl 64 mink lung epithelial cells. We investigated the regulation of TGF-beta 1 receptor by 4 kinds of growth factor: epidermal growth factor (EGF) but not TGF-beta 1, insulin or insulin-like growth factor-1 increased the level of TGF-beta 1 binding sites in a concentration- and time-dependent manner. These findings suggest that TGF-beta 1 may be a potential autocrine growth factor in a human endometrial cancer cell line IK-90 and that this autocrine mechanism may be affected by EGF.
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PMID:Autocrine growth mechanism by transforming growth factor (TGF)-beta 1 and TGF-beta 1-receptor regulation by epidermal growth factor in a human endometrial cancer cell line IK-90. 839 35

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

The biological significance of epidermal growth factor (EGF)-related proteins in the development and progression of endometrioid endometrial carcinoma was studied. Expression of EGF-related proteins including EGF, transforming growth factor-alpha (TGF-alpha), cripto (CR), amphiregulin (AR), and EGF receptor (EGFR) were immunohistochemically examined. Results were then correlated with clinicopathologic findings and steroid receptor status in 12 specimens with normal endometrium, 13 with endometrial hyperplasia, and 40 with endometrioid endometrial carcinoma. EGFR, EGF, TGF-alpha, and CR immunoreactivities were observed in 58.3%, 66.7%, 91.6%, and 66.7% of normal endometrial specimens; 100%, 15.4%, 100%, and 30.8% of endometrial hyperplasia specimens; and 67.5%, 32.5%, 65.0%, and 65.0% of endometrial carcinoma specimens, respectively. AR immunoreactivity was not observed in any of the normal, hyperplastic, or neoplastic endometrium. The presence or absence of EGFR or TGF-alpha in endometrial carcinoma correlated with surgical stage, depth of myometrial invasion, and findings from peritoneal washing cytology. EGF expression significantly correlated with the age of the patients and that of CR with surgical stage and peritoneal washing cytological findings. There was a significant correlation between EGFR and TGF-alpha expression, and between EGF and TGF-alpha. Co-expression of EGFR and TGF-alpha, EGFR and CR, and TGF-alpha and CR in carcinoma specimens significantly correlated with advanced surgical stage, deeper myometrial invasion, and positive peritoneal washing cytology. In normal as well as hyperplastic endometrium, endometrial glands immunohistochemically positive for TGF-alpha were generally positive for ER, but in poorly differentiated endometrial carcinoma, cells positive for TGF-alpha tended to be negative for ER. The results of the present study show that among EGF-related proteins, expression of TGF-alpha and CR seem to be associated with the progression of human endometrioid endometrial carcinoma. Additionally, expression of TGF-alpha became increasingly estrogen independent with increasing histological carcinoma grades.
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PMID:Expression of epidermal growth factor family proteins and epidermal growth factor receptor in human endometrium. 860 44

The mouse lactoferrin gene responded to forskolin, 12-O-tetradecanoyl phorbol-13-acetate, and epidermal growth factor (EGF) stimulation via two adjacent enhancer elements, the cAMP response element (CRE) and EGF response element (EGFRE), collectively referred to as the mitogen response unit. In this report, we examined the minimal promoter and enhancer elements of the mouse lactoferrin gene that are required for EGF-induced transcriptional activation. We found that the CRE and noncanonical TATA box (ATAAA) are the minimal promoter elements for basal activity of the chloramphenicol acetyltransferase (CAT) reporter construct whereas the EGFRE is needed for an additional activity induced by EGF in transiently transfected human endometrial carcinoma RL95-2 cells (RL95-2). The EGFRE, however, did not function in heterologous promoters [SV 40 and thymidine kinase (TK)]. Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. In transiently transfected cells, EGF and forskolin showed synergistic effects on the CAT reporter that contained both response elements. Mutation made at either element or insertion of extra nucleotides between the two elements severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells formed three complexes (A, B, and C) with the oligonucleotides containing both EGFRE and CRE in electrophoretic mobility shift assay. A new complex (E) was detected with the nuclear protein of EGF-treated cells. By oligonucleotide competition experiments, we demonstrated that the complex E was generated by protein bound to CRE. EGF-induced binding activity could be abolished by calf intestinal alkaline phosphatase but not by the protein synthesis inhibitor, cycloheximide. Therefore, binding of a preexisting phosphoprotein to the CRE region could be one of the requirements for EGF-induced mouse lactoferrin gene promoter activity.
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PMID:Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements. 877 33

In a total of 113 cases of endometrial neoplasm, we studied the immunohistochemical expression of estradiol (E2), epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and epidermal growth factor receptor (EGFR). Positive immunoreactivity of E2 was found in 61% of the neoplasms. E2 immunoreactivity correlated well with high histologic grade and early clinical stage. Positive immunoreactivity for EGF or EGFR was found in 25.6% or 53.1% of the neoplasms, respectively. However, this was unrelated to histologic grade or clinical stage. On the other hand, TGFalpha immunoreactivity was found in 67% of endometrial neoplasias and was correlated with poor histologic grade and advanced stage. Contingency tables indicated a significant negative association between the status of E2 and that of TGFalpha. Simultaneous expression of E2, EGF and EGFR, or E2, TGFalpha and EGFR was found in 6.8% and 15.9% of endometrial carcinomas, respectively. These results suggest that a predominant number of endometrial carcinomas escape autocrine/paracrine growth regulation by EGF and E2 or TGFalpha and E2, and that TGFalpha may be involved in the progression of endometrial carcinoma.
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PMID:Immunohistochemical study of estradiol, epidermal growth factor, transforming growth factor alpha and epidermal growth factor receptor in endometrial neoplasia. 900 45

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