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 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.
Mol Endocrinol 1996 Jun
PMID:Promoter-specific activation of mouse lactoferrin gene by epidermal growth factor involves two adjacent regulatory elements. 877 33

The estrogen receptor has been successfully targeted with the anti-estrogen tamoxifen to treat all stages of breast cancer. Because tamoxifen is a partial agonist, it exhibits target-site specificity: it acts as an anti-estrogen in the breast to inhibit tumor growth, while exhibiting estrogenic effects on bones and lipid metabolism. Therefore, tamoxifen has the added benefit of maintaining bone density and reducing the risk of myocardial infarction in postmenopausal women. However, undesirable side effects of tamoxifen preclude its use as a hormone replacement therapy for otherwise healthy women. New anti-estrogens are currently being developed that may prevent osteoporosis, breast and endometrial cancer, and reduce the risk of myocardial infarction.
Mol Med Today 1996 May
PMID:Targeted anti-estrogens to treat and prevent diseases in women. 879 91

Human genital skin fibroblasts contain both the full-length 110 K androgen receptor protein (AR-B, apparent M(r) approximately 110,000) and an 87 K N-terminally truncated AR isoform (AR-A, apparent M(r) approximately 87,000). These two AR species are structurally analogous to the A- and B-isoforms of the progesterone receptor (PR). We examined the distribution pattern of human AR isoforms in a variety of fetal and adult tissues by Western blot analysis. Relative levels of immunoreactive AR proteins in high salt tissue extracts were estimated by densitometry in comparison to a standard normal genital skin fibroblast preparation. High AR levels (AR-A + AR-B = 0.8-7.7) were present in male and female reproductive tissues from mid-trimester fetuses, including penis, prostate, testis, epididymis, scrotal skin, labial skin, uterus/cervix, and ovary. AR-A and AR-B (0.08-0.9) also were found in 14 non-genital fetal tissues (bladder, fat, lung, great vessel, trachea, muscle, scalp skin, kidney, thyroid, intestine, thymus, ureter, stomach and rectum). AR-A accounted for 4-26% of the AR protein detected in these tissues. Ten other fetal tissues had low levels of AR-B (0.02-0.3) and little or no detectable AR-A. AR-B also was the predominant or only immunoreactive AR species found in 17 adult human tissues. AR levels in adult reproductive tissues (prostate, endometrium, ovary, uterus, fallopian tube, testis, seminal vesicle, myometrium, and ejaculatory duct) ranged from 0.1 to 2.2. Immunoreactive AR (0.4-0.8) also was present in specimens of prostate carcinoma, endometrial carcinoma, thyroid carcinoma and kidney. Lower levels of AR (0.03-0.1) were detected in adult breast, colon, lung and adrenal gland specimens. This study demonstrates that immunoreactive AR protein is present in a wide variety of human fetal and adult tissues and that two AR isoforms are expressed in many tissues.
Mol Cell Endocrinol 1996 Jun 18
PMID:A and B forms of the androgen receptor are expressed in a variety of human tissues. 880 38

The observation that charcoal-treated fetal bovine serum (ctFBS) was able to modify one of main pathways of estrogens in cancer cells in culture, prompted us to initiate the present study. The active component of serum was isolated using native preparative polyacrylamide gel electrophoresis (PAGE). Under analysis with SDS-PAGE, a M(W) of 68 kDa and mobility of authentic bovine serum albumin (BSA) was observed. The addition of BSA to the serum free culture medium of HEC 1A human endometrial cancer cell line, resulted in an alteration of estradiol (E2) metabolism similar to that observed in the presence of ctFBS. BSA in fact, much enhanced 16 alpha-hydroxylation and significantly reduced 2-hydroxylation of E2 in HEC 1A cells. Comparable results were obtained with different endometrial (Ishikawa) and mammary (MCF-7) tumor cell lines having a different metabolic conversion rate of E2. Several albumin preparations from either bovine or human serum had the same effect; besides, BSA activity was unaffected by treatment with dextran-charcoal or heat. In the light of the present results, the inclusion of serum albumin (SA) in the formulation of media for studies evaluating steroid metabolism in cultured cells should be carefully considered.
Mol Cell Endocrinol 1995 Dec 29
PMID:Effect of serum albumin on estrogen metabolism in human cancer cell lines. 882 98

We have previously demonstrated that lactoferrin (LF) is a major estrogen-inducible protein in the mouse uterus. The increase of LF mRNA after estrogen treatment (> 300 fold) is the result of a complex interplay among transcription factors acting on the estrogen response element (ERE) of the LF gene. Two transcription factors-the estrogen receptor (ER) and the chicken ovalbumin upstream promoter transcription factor (COUP-TF)-play opposing roles in the estrogen responsiveness of the LF gene promoter-reporter constructs in transiently transfected human endometrial carcinoma cells. The ratio of ER/COUP-TF in the transfected cells appears to be critical for estrogen-stimulated LF gene promoter activity (Liu et al, 1993). In the current study, ER and COUP-TF mRNA levels are examined and related to LF mRNA expression in various mouse tissues, including the developing uterus with/without estrogen stimulation. Results show that LF mRNA and protein are expressed in various tissues during development, but the potent synthetic estrogen, diethylstilbestrol (DES), does not increase LF mRNA expression in nonreproductive tissues such as liver, spleen, and lung. In contrast, in developing neonatal reproductive tract tissues, DES increases LF mRNA and protein expression as previously reported in immature and mature uterine tissues. DES, however, did not affect ER and COUP-TF expression in developing uterine tissues. Although the uterus has a high ratio of ER/COUP-TF as compared to other tissues examined, COUP-TF may not be the only regulator for LF gene expression in this particular tissue since COUP-TF remains constant during development and following DES treatment. These data point to the complexity of differential expression of LF gene in estrogen responsive and nonresponsive tissues during development.
Mol Reprod Dev 1996 Sep
PMID:Estrogenic effect on the expression of estrogen receptor, COUP-TF, and lactoferrin mRNA in developing mouse tissues. 887 65

The estrogen receptor (ER) contains two transcriptional activation domains: AF-1 and AF-2. AF-2 is dependent on a highly species-conserved region of the ER. It has been shown that site-directed point mutations of conserved hydrophobic amino acids within this region reduce estrogen-dependent transcriptional activation. In addition, when these mutated ERs are transfected into HeLa cells, both tamoxifen and ICI 164,384 become strong agonists. The implication is that mutations in this region could account for the tamoxifen-stimulated tumors seen clinically. We performed single stranded conformational polymorphism (SSCP) analysis spanning the entire ER along with DNA sequencing of the AF-2 region of the ER isolated from two different tamoxifen-stimulated breast cancers, MCF-7/TAM and MCF-7/MT2, and a tamoxifen-stimulated endometrial cancer, EnCa 101. In addition, a tamoxifen-stimulated endometrial carcinoma cell line, the Ishikawa cell line, was also studied. There were no mutations found by SSCP analysis and sequencing of all four AF-2 regions also revealed no mutations. Mutations within the AF-2 region of the human ER do not appear to account for the growth of human breast and endometrial carcinomas that are used as reproducible laboratory models of tamoxifen-stimulated growth observed clinically.
J Steroid Biochem Mol Biol 1996 Aug
PMID:An analysis of tamoxifen-stimulated human carcinomas for mutations in the AF-2 region of the estrogen receptor. 891 73

To know the effects of sex steroids on the potentials of growth, invasion, and metastasis with neovascularization of endometrial cancer, the expression of plasminogen activator inhibitor (PAI)-1 [an inhibitor of tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA)] and its mRNA in well-differentiated uterine endometrial cancer cell line Ishikawa was determined by an enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction-Southern blotting (RT-PCR-SB), respectively, under the influence of sex steroids. In Ishikawa cells, either estradiol or progestins (progesterone, medroxyprogesterone acetate, or 17 alpha-hydroxyprogesterone alone) induced the expression of PAI-1 and its mRNA, and those expressions were increased approximately two-fold by both estradiol and progestin administered together. Therefore, sex steroidal induction of PAI-1 might contribute to the inhibition of invasion and metastasis, concomitantly with the inhibition of neovascularization associated with tPA and uPA activities, in well differentiated endometrial cancer.
J Steroid Biochem Mol Biol 1996 Sep
PMID:Sex steroids regulate the expression of plasminogen activator inhibitor-1 (PAI-1) and its mRNA in uterine endometrial cancer cell line Ishikawa. 900 32

We have compared the cell and tissue selective estrogenic and antiestrogenic activities of tamoxifen, raloxifene, ICI 164,384 and a permanently ionized derivative of tamoxifen--tamoxifen methiodide (TMI). This non-steroidal antiestrogen has limited ability to cross the blood brain barrier and is therefore less likely to cause the central nervous system disturbances caused by tamoxifen. We have used the stimulation of the specific activity of the "estrogen induced protein", creatine kinase BB, as a response marker in bone, cartilage, uterine and adipose cells and in rat skeletal tissues, uterus and mesometrial adipose tissue. In vitro, TMI, tamoxifen and raloxifene mimicked the agonistic action of 17beta-estradiol in ROS 17/2.8 rat osteogenic osteosarcoma, female calvaria, and SaOS2 human osteoblast cells. In Ishikawa endometrial cancer cells, tamoxifen showed reduced agonistic effects and raloxifene showed no stimulation. However, as antagonists, tamoxifen and raloxifene were equally effective in Ishikawa or SaOS2 cells. In immature rats, all four of the antiestrogens inhibited estrogen action in diaphysis, epiphysis, uterus and mesometrial adipose tissue; when administered alone, tamoxifen stimulated creatine kinase (CK) specific activity in all these tissues. Raloxifene and TMI, however, stimulated only the skeletal tissues and had no stimulatory effect in the uterus or mesometrial fat, and the pure antiestrogen ICI 164,384 showed no stimulatory effect in any of the tissues. The simultaneous injection of estrogen, plus an antiestrogen which acted as an agonist, resulted in lower CK activity than after injection of either agent alone. These differential effects, in vivo and in vitro, may point the way to a wider therapeutic choice of an appropriate antiestrogen which, although antagonizing E2 action in mammary cancer, can still protect against osteoporosis and cardiovascular disease and not stimulate the uterus with its attendant undesirable changes, or interfere with the beneficial action of E2 in the brain.
J Steroid Biochem Mol Biol 1996 Dec
PMID:Tissue selective action of tamoxifen methiodide, raloxifene and tamoxifen on creatine kinase B activity in vitro and in vivo. 901 Mar 44

Human endometrium undergoes sequential changes during the menstrual cycle and becomes receptive to implantation during a defined period in the secretory phase. We attempted to identify the genes expressed during this period by representational difference analysis (RDA). When the cDNAs of a proliferative endometrium were used as the driver and the cDNAs of a post-ovulatory day 5 endometrium were used as the tester, a number of bands were identified by RDA. DNA of the cloned RDA products revealed that the majority of the clones contained a fragment of a cDNA identical to that of a crystallin B chain. Northern blot analysis showed that the expression of the alpha crystallin B chain mRNA was absent during the proliferative phase. The expression of the mRNA of alpha crystallin B chain first appeared in the secretory phase, progressively increased during this phase and peaked in the late secretory endometria. The pattern of expression of alpha crystallin B chain mRNA in the endometrium of mature cycling baboons (Papio anubis) was similar to that seen in human endometrium. As revealed by Western blot analysis, the expression of the alpha crystallin B chain protein in human endometrium followed a pattern of expression similar to its mRNA. At the cellular level, the immunoreactive protein first appeared in the surface epithelial cells of human endometrium within the implantation window without significant immunoreactivity in the underlying glandular cells. During the mid- and late secretory phases, the intensity of staining in the epithelial cells was enhanced and an intense immunoreactivity was developed in the glandular epithelium, alpha crystallin B chain was virtually an epithelial product and no immunoreactivity for this protein was detectable in the stromal cells, endothelial cells or lymphoid cells. The expression of alpha crystallin B chain could be regulated, by medroxy progesterone acetate as well as by oestrogen withdrawal, in human endometrial carcinoma cells (EnCa-101), transplanted to nude mice. Based on the data presented here, the known function of alpha crystallin B chain and its distinct pattern of expression in human endometrium, we suggest that this protein is an important factor within the molecular repertoire that makes endometrium receptive to implantation.
Mol Hum Reprod 1997 Apr
PMID:The progressive rise in the expression of alpha crystallin B chain in human endometrium is initiated during the implantation window: modulation of gene expression by steroid hormones. 923 61

In order to test the hypothesis that integrin and uteroglobin (UG) expression in cultured endometrial cells are affected by hormone treatment, Ishikawa-CH endometrial cancer cells were cultured and exposed to oestradiol or oestradiol and progesterone regimens and assayed using immunohistochemistry. We evaluated the intensity of immunohistochemical staining for the integrin monomers alpha(v) and beta1, the dimers alpha(v)beta3 and alpha(v)beta6, and for the secretory protein uteroglobin under various experimental conditions. Cells grown in control media stained positively for the integrin monomers alpha(v) and beta1, the dimer alpha(v)beta3, and for UG. Oestradiol and sequential oestradiol/progesterone reversibly suppressed staining for the dimer alpha(v)beta3. Hormone treatment had no effect on the staining of the beta1 and alpha(v) monomers or UG. The alpha(v)beta6 dimer antibody did not stain under any experimental treatment conditions. These data indicate that expression of the integrin complex alpha(v)beta3 is reversibly suppressed by oestradiol in Ishikawa cells and that these cells may be a good model for studying hormone-driven molecular changes in endometrium.
Mol Hum Reprod 1997 Jul
PMID:Modulation of implantation-associated integrin expression but not uteroglobin by steroid hormones in an endometrial cell line. 926 33


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