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)

The molecular genetics of human endometrial carcinoma have yet to be defined to any significant extent. Cell lines from 11 endometrial carcinomas were examined for alterations in proto-oncogenes that might predictably be present, based on existing data from the better-characterized human carcinomas of the uterine cervix, ovary, and breast. Codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes were examined for possible point mutations, and the c-erbB2/neu, c-myc, and epidermal growth factor receptor (EGFR) genes were examined for amplification or overexpression. Ras mutations were found in seven of 11 (64%) tumors, including three in codon 61 of Ha-ras (CAG----CAT) and four in codon 12 of Ki-ras (GGT----GAT in two and GGT----GTT in two). No evidence was found for amplification or overexpression of the c-erbB2 or EGFR genes in any tumor. One tumor contained amplified c-myc sequences and exhibited relative overexpression of c-myc. These data suggest that the amplification or overexpression of several proto-oncogenes frequently observed in other human gynecologic and breast tumors are not prevalent in endometrial carcinoma and that ras gene mutations are relatively common in this tumor type.
 ...
PMID:Analysis of oncogene alterations in human endometrial carcinoma: prevalence of ras mutations. 206 24

The precursor of cathepsin D, a lysosomal acidic protease, is secreted by human breast cancer cells, where its synthesis is specifically induced by estrogens and growth factors. In this study, we investigated the hormonal regulation of cathepsin D and its mRNA in uterine cells. In the Ishikawa endometrial cancer cell line, epidermal growth factor (EGF) increased the level of cathepsin D and its mRNA 2- to 3-fold. Although expression of the transiently transfected estrogen-responsive recombinant (Vit. tk. CAT) and the endogenous progesterone receptor was markedly increased by estradiol in Ishikawa cells, estradiol did not alter the level of cathepsin D or its mRNA. The progestin R5020 induced the expression of the LTR sp65 CAT, which contains the progesterone-responsive element of the MMTV but it too was without effect on cathepsin D. By contrast, the expression of cathepsin D gene, in normal rat uterus, was increased by R5020 but not by estradiol. We conclude that cathepsin D gene expression is regulated differently by sex steroid hormones in endometrial and breast cancer cell lines, whereas it is similarly induced by EGF in these cells.
 ...
PMID:Differential regulation of cathepsin D by sex steroids in mammary cancer and uterine cells. 261 33

HEC1A endometrial cancer cells express the wild-type form of the estrogen receptor (ER) and 17beta-estradiol (E2) induces proliferation of these cells. In contrast, tamoxifen only causes a minimal increase (<20%) in cell proliferation. In HEC1A cells transiently transfected with the C3-Luc plasmid derived from the complement C3 gene, both E2 and tamoxifen exhibited ER agonist activity and tamoxifen was also a partial antagonist for this response. The relative ER agonist/antagonist activities of E2, tamoxifen and ICI 182,780 were also investigated in HEC1A1 cells transiently transfected with two E2-responsive plasmids, pCATHD-CAT and pCKB-CAT which contain 5'-promoter inserts from the cathepsin D and creatine kinase B genes, respectively. The results showed that E2 and tamoxifen induced reporter gene activity in cells transiently transfected with both constructs. ICI 182,780 exhibited partial ER agonist activity only in cells transiently transfected with pCKB-CAT and antagonized E2-induced reporter gene activity using both the CKB- and CATHD-derived constructs. These results demonstrate that HEC1A endometrial cancer cells are E2-responsive and represent a useful cell culture model for understanding hormone/antihormone-induced endometrial cell responses.
 ...
PMID:Estrogen- and antiestrogen-responsiveness of HEC1A endometrial adenocarcinoma cells in culture. 961 30

Expression of the lactoferrin gene in a variety of tissues is regulated differentially. We have previously demonstrated that the lactoferrin gene is regulated by estrogen and mitogen in mouse uterus. The mouse lactoferrin gene responded to forskolin, cAMP, TPA and EGF stimulation via two adjacent enhancer elements, the CRE and EGFRE and collectively referred to as the Mitogen Response Unit (MRU). We found that CRE is responsible for forskolin, cAMP and TPA whereas EGFRE is for EGF stimulation. 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 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 TK). Therefore, EGF-stimulated lactoferrin gene activity is promoter specific in RL95-2 cells. Mutation made at either elements or insertion of extra nucleotides between the two elements, severely affected EGF-stimulated activity. Nuclear protein prepared from RL95-2 cells protected the EGFRE, CRE and noncanonical TATA from DNAase I digestion in a footprinting analysis. Nuclear protein which interacted with the CRE were previously identified as API and CREB. In this study, we isolated a cDNA clone from an RL95-2 expression library that encodes the EGFRE binding protein. Partial sequence of the cDNA clone revealed 100% nucleotide identity with a GC-box binding protein, BTEB2. Protein-protein interaction among the transcription factors could fine-tune the mouse lactoferrin expression in various tissues.
 ...
PMID:Mouse lactoferrin gene. Promoter-specific regulation by EGF and cDNA cloning of the EGF-response-element binding protein. 978 44