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

The sensitivity to medroxyprogesterone acetate (MPA) and tamoxifen (T) and their combination was assayed in 13 patients with untreated endometrial cancer by an in vitro ATP-bioluminescence method. The method measures the levels of adenosinetriphosphate (ATP), the basic energy source of living cells. A tumor was considered to respond to the drug, if the proportion of living cells after manipulation was 50% or less from unmanipulated control culture. Estrogen (ER) and progesterone (PR) receptors were assayed by the DCC-method and the results calculated by Scatchard-analysis. ER (greater than or equal to 3 fmol/kg cytosol protein) was present in all tumors and PR (greater than or equal to 10 fmol/kg cytosol protein) in 85% of the tumors. The response rate in vitro to MPA was 67% (8 out of 12 tumors), to T 18% (2 out of 11) and to their combination 69% (9 out of 13). The G1 tumors responded statistically significantly better to MPA (p less than 0.01) and MPA + T (p less than 0.02) as compared to T. MPA produced higher cell kill of G1 than G2 tumors (p less than 0.05). The ER content correlated with the effect of MPA in vitro in 67%, with the effect of T in 18% and with that of their combination in 69% of the tumors. The PR content correlated with the effects of MPA in vitro in 83%, with the effect of T in 36% and with that of their combination in 54% of the tumors. It was concluded that the in vitro ATP-bioluminescence method provides valuable information besides steroid receptor determinations for sensitivity testing of endometrial cancer to hormones.
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PMID:Steroid receptors and response of endometrial cancer to hormones in vitro. 295 89

The sex steroid hormone receptor levels of uterine cytosol were assayed in the course of experimental induction of endometrial carcinoma in rats. Effects of administration of various hormones on the receptor levels were examined with each histological pattern of endometrium. 1) The dissociation constants for E2 and R5020 bindings with uterine cytosol were almost fixed in spite of various histological patterns of endometrium. 2) The influence of administrated hormones on the receptor assay system could be neglected by the preincubation of uterine cytosol with DCC for five times. 3) By the administration of DES for six weeks, estrogen receptor levels were increased significantly in adenocarcinoma, while progesterone receptor levels did not show the tendency of decreasing. 4) By the administration of MPA combined with DES, estrogen receptor levels were not decreased significantly in both atypical adenomatous hyperplasia and adenocarcinoma; progesterone receptor levels were decreased in all groups. 5) By the administration of MPA, estrogen receptor levels were decreased significantly in adenocarcinoma. These data suggest that receptor levels can be controlled by the administration of sex hormones in the course of development of endometrial carcinoma.
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PMID:[Changes of sex steroid hormone receptors in rat uterine cytosol during experimental induction of endometrial carcinoma (author's transl)]. 645 22

The cytoplasmic concentrations of ER, AR, PR, and GR were determined in 124 specimens of normal and abnormal endometrium and other uterine human tissues by the DCC technique. In the endometrial carcinoma group, we observed that pretreatment with MAP leads to low cellularity, higher amount of AR, lower amounts of detectable ER, GR, and PR: the last receptor was almost always absent. A positive correlation between ER presence and tumor grade of differentiation was found in endometrial tumors from hormone-untreated patients. With the value of 142 fmol/mg DNA as the cut off point between high and low binding capacity, the frequency of the single receptors within the hormone-untreated cancer group ranged from 61% to 88%; ER and PR were simultaneously present in 55% of cases (they are tightly correlated in the different biopsies with respect to frequency and amount); ER-AR-PR were present in 45% and all the four receptors in 40% of cases. Slightly higher values were found in normal endometrium collected from hormone-untreated patients.
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PMID:Multiple steroid hormone receptors in normal and abnormal human endometrium. 721 81

Presumptive tumor suppressor genes may be localized to specific chromosomes by the procedure of microcell fusion, whereby individual chromosomes derived from normal human cells are introduced into tumor cells. Allelic loss on chromosome 18 is commonly seen in endometrial carcinoma, and the DCC gene on chromosome 18q is a potential human tumor suppressor gene. In this study, we investigated the hypothesis that a gene on chromosome 18, possibly DCC, is capable of suppressing the tumorigenicity of endometrial carcinoma cells. Microcells from the mouse A9 cell clone containing one human chromosome 18 tagged with the pSV2-neo plasmid were fused with the highly tumorigenic endometrial carcinoma cell lines HHUA and Ishikawa, and G418-resistant microcell hybrids containing and extra copy of chromosome 18 were isolated. Clones isolated from the HHUA cell line were completely suppressed for tumorigenicity in nude mice, and clones from the Ishikawa line were suppressed or inhibited for tumorigenicity. In contrast, growth rates in vitro were not significantly affected in clones from either parental cell line. DCC expression was elevated in most of the suppressed hybrids. These results indicate that a gene on human chromosome 18 is capable of suppressing the tumorigenicity of endometrial carcinoma cells, and that DCC is a candidate for this endometrial carcinoma tumor suppressor gene.
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PMID:Suppression of endometrial carcinoma cell tumorigenicity by human chromosome 18. 754 39

We compared concentrations of cytosolic estrogen receptors (ERc) measured in 35 postmenopausal endometrial carcinomas by ligand binding method (LBA) (dextran-coated charcoal assay) and enzyme immunoassay (EIA). Correlations between ERc, nuclear estrogen receptors (ERn) determined by EIA, and cytosolic progesterone receptors (PR) measured by LBA were also studied. While ERc concentrations determined by LBA and EIA were highly correlated (r: 0.94), ERc values detected by LBA were approximately twice those found by EIA (median values of ERc: 155 vs. 64 fmol/mg cytosol protein, DCC vs. EIA). The percentages of ERc positive tumors were 89% by LBA and 77% by EIA. The median fraction of total ER present as ERn was 63%. PR levels correlated positively with ERn concentrations (r: 0.73). We explore possible reasons why greater concentrations of ERc are determined by estradiol binding than by the ER-EIA kit in endometrial cancer.
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PMID:Estrogen receptor determination in endometrial carcinoma: ligand binding assay versus enzyme immunoassay. 776 51

In order to identify the possible role of the DCC gene in neoplasms of the human female reproductive tract, messenger RNA expression of the DCC gene was examined by reverse transcriptase-polymerase chain reaction, and expression of the DCC gene product was detected immunohistochemically. While histologically normal endometrium, cervical epithelium and ovary expressed detectable mRNA of the DCC gene, three of eight (37%) endometrial carcinomas, one of two (50%) cervical carcinomas and 9 of 22 (41%) ovarian malignant tumours had significantly reduced or negligible DCC expression, and another endometrial carcinoma and two other ovarian tumors underexpressed DCC when compared with histologically normal endometrial or ovarian tissues. Impaired DCC mRNA expression was detected more frequently in grade 3 ovarian epithelial tumours than in grade 1 tumours (P = 0.002). Loss of expression of the DCC gene product detected by immunohistochemistry significantly correlated with the loss of mRNA expression in ovarian carcinomas (P = 0.01 by chi-square test) or in both endometrial and ovarian carcinomas combined (P = 0.001). Loss of heterozygosity of the DCC gene was also evaluated by restriction fragment polymorphism analysis of the polymerase chain reaction-amplified DNA fragment. Loss of heterozygosity of the DCC gene was detected in one of seven (14%) informative cases of endometrial carcinomas, 1 of 11 (9%) informative cases of cervical carcinomas and two of six (33%) informative cases of ovarian tumours. These results demonstrate that inactivation of the DCC gene, especially by the loss of expression, plays a significant role in the aetiology of neoplasms of the human reproductive tract.
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PMID:Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive tract. 788 Jul 25

DCC (Deleted in Colorectal Carcinoma) is a candidate tumor suppressor gene located on the long arm of chromosome 18. DCC was initially identified and cloned during a search for the target gene located in a region of 18q that demonstrated loss of heterozygosity (LOH) in 70 to 80% of colorectal cancers. More recently, the region of 18q harboring the DCC gene has been shown to undergo LOH in approximately 14 to 30% of endometrial carcinomas. These findings suggest that DCC may be a target of LOH in at least some endometrial carcinomas and, therefore, may have a role in the pathogenesis of this common malignancy of the female genital tract. To address this possibility, we analyzed 26 cases of endometrioid endometrial carcinoma for DCC LOH and alterations in an AT microsatellite repeat located in an intron of the DCC gene. LOH was detected in one case (4%). Allelic shifts at the DCC AT repeat were detected in five (19%) additional cases. We also evaluated DCC protein expression by immunohistochemical analysis in normal, hyperplastic, and neoplastic endometrial tissues. Three proliferative and five secretory endometria and one simple endometrial hyperplasia demonstrated staining for DCC. Four of the 26 endometrioid endometrial carcinomas for which frozen tissue was available, including at least one from each histologic grade, and a case of endometrioid carcinoma confined to the endometrium completely lacked detectable staining for DCC. Although DCC LOH was infrequent in endometrial carcinomas, alterations of the gene (LOH or AT repeat alterations) were not uncommon (23% of our cases). In addition, DCC was expressed in normal endometrial tissue, whereas expression was lost in all of the five endometrial carcinomas. The combination of the genetic alterations and loss of DCC protein expression suggests that inactivation of the DCC gene may play a role in the pathogenesis of endometrial carcinoma.
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PMID:DCC genetic alterations and expression in endometrial carcinoma. 902 25

To obtain functional evidence for DCC as a tumour suppressor associated with endometrial cancer, the human DCC cDNA encoding a complete open reading frame (ORF) was transfected into highly tumorigenic human endometrial carcinoma cells, HHUA and Ishikawa in which DCC expression was completely deleted. Reconstituted expression of DCC in HHUA had little effect on in vitro growth, but suppressed tumour formation in mice completely. The clones from Ishikawa had abundant DCC expression similar to that in normal endometrium. Their growth in vitro was suppressed and showed apoptotic phenotype. Lower levels of DCC expression in the prolonged passaged clones did not induce apoptosis, but still had the potential to suppress tumorigenicity. These observations imply a role of DCC in regulation of normal endometrial cell growth, and categorize DCC as the tumour suppressor gene for endometrial cancer.
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PMID:Suppressed tumorigenicity of human endometrial cancer cells by the restored expression of the DCC gene. 1064 5

Alterations in the cellular genome affecting the expression or function of genes controlling cell growth and differentiation are considered to be the main cause of cancer. Genes that cause cancer are of two distinct types: oncogenes and onco-suppressor genes. The normal proto-oncogene can be converted into an active oncogene by deletion or point mutation in its coding sequence, gene amplification, and by specific chromosome rearrangements. Mutations and abnormal expression in ras, myc, c-erbB-2, and other oncogenes have been reported in several types of gynecological cancer. Onco-suppressor genes are involved in gynecological cancer, their functions are localized in different phases of the cell cycle. Structural changes and deletions of these genes can cause cancer. Mutations in the p53, BRCA1, DCC, and PTEN genes have been reported in gynecological cancers such as ovarian, cervical, and endometrial cancer. Human papillomaviruses are of major interest because specific types (HPV-16, -18, and several others) have been identified as causative agents in at least 90% of cancers of the cervix. In this study we summarize the available information regarding the implication of specific oncogenes, onco-suppressor genes, and HPV in the development of female genital malignancies.
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PMID:Molecular basis of gynecological cancer. 1081 92