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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcriptional activity of human estrogen receptor (hER) gene was modulated by competition with double-stranded PCR-generated DNA fragments (decoys) that contain 5' upstream sequences of the hER gene. Two DNA fragments belonging to the P1 canonical promoter and the P3 distal promoter, 120 and 102 bp in size respectively, were produced by PCR and directly transfected in MCF7 breast cancer cells. After 24 hours transfection, RT-PCR analysis revealed that the 120 bp decoy significantly reduced the expression of the ER gene and estrogen responsive genes (PR and c-myc), whereas the 102 bp decoy increased the ER mRNA level. An ER unrelated PCR product, used as control, had no activity. The biological activity of these ds DNAs was related to their high stability, binding affinities, and lack of cytotoxicity. These findings suggest that such PCR product decoys may be a non-antisense tool to analyze putative regulatory sequences and to study the function of DNA-binding transcription factors.
Breast Cancer Res Treat 1998 Jun
PMID:Modulation of estrogen receptor gene expression in human breast cancer cells: a decoy strategy with specific PCR-generated DNA fragments. 977 6

A quantitative nucleic acid hybridization assay for determination of estrogen receptor (ER) mRNA in breast carcinoma is described. The assay, which is based on the branched DNA (bDNA) technology, requires 20 mg of tissue, is simple, highly specific, and reproducible, and correlates reasonably well with an established methodology (r = 0.87). The assay has a dynamic range of 3 x 10(3)-6 x 10(7) copies of ER mRNA per well. ER message as high as 2.5 x 10(6) copies per well could be detected in normal breast tissues. Thus a sensitivity of 3 x 10(3) ER copies per well was sufficient to analyze clinical specimens. In the present studies, accurate measurement of tissue weight enabled direct reporting of the ER mRNA values as the end point results. The bDNA assay provides a useful tool for the detection and quantitation of ER mRNA in research and routine clinical laboratories.
Breast Cancer Res Treat 1998 Jul
PMID:Quantitation of estrogen receptor mRNA in breast carcinoma by branched DNA assay. 980 19

To gain insight into the possible biological role of variant estrogen receptor (ER) expression in human breast cancer, we have undertaken a study to determine if the expression of the clone 4 variant ER mRNA was associated with markers of either reduced endocrine sensitivity [i.e., progesterone receptor (PgR) negativity] or a poor prognosis (node positivity, large tumor size, and high percentage S-phase fraction). mRNA levels of clone 4 variant ER and wild-type (WT) ER were assayed by RNase protection assay in 106 breast cancer specimens. The tumors comprised two major groups: "good" prognosis and "poor" prognosis based on several conventional biological prognostic features. Each group was divided into three subgroups (ER+/PgR+, ER+/PgR-, and ER-/PgR-). WT and clone 4 variant ER mRNAs were undetected in ER-/PgR- tumors. We determined that clone 4 variant ER mRNA levels varied proportionately with WT mRNA levels, and regression analysis was used to determine if the amount of clone 4 variant ER mRNA relative to WT was associated with prognosis or PgR content. Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in tumors with markers of poor prognosis compared to those with markers of good prognosis (P = 0.0004). Significantly higher levels of clone 4 variant ER mRNA relative to WT were found in PgR- tumors compared to PgR+ tumors (P = 0.011). Such data are consistent with an association of clone 4 variant ER mRNA expression with progression of human breast cancer from hormone dependence to independence.
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PMID:Relationship of clone 4 estrogen receptor variant messenger RNA expression to some known prognostic variables in human breast cancer. 981 68

The CCND1 gene, encoding the cell cycle regulatory protein cyclin D1, maps to chromosome 11q13, a locus that is amplified in about 13% of breast cancers. Because several studies have indicated a relationship between 11q13 amplification and markers of phenotype including estrogen receptor (ER) status, we tested the relationship between CCND1 and ER gene expression in 364 primary breast cancers using Northern blot analysis. Seventy-three % of samples were positive for ER mRNA, and cyclin D1 mRNA levels in the ER-positive group were significantly higher than those in the ER-negative group (P = 0.0001). When the samples were divided into quartiles of cyclin D1 expression, 58% of samples were ER positive in the lowest quartile and 87% in the highest quartile. The tumors expressing the highest levels of cyclin D1 (7%) were all ER positive. Furthermore, ER mRNA levels in the half with lower cyclin D1 mRNA were significantly less than in the half with higher cyclin D1 levels (P = 0.0001). Using simple regression analysis, there was a significant positive correlation between cyclin D1 and ER mRNA levels in the total population (P = 0.0001). This study demonstrates that cyclin D1 mRNA and ER mRNA are positively correlated in primary breast cancer, but the functional relationship between these genes remains to be elucidated.
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PMID:Cyclin D1 and estrogen receptor messenger RNA levels are positively correlated in primary breast cancer. 981 51

The critical mechanisms responsible for antiestrogen resistance have not yet been elucidated. We previously established a breast cancer cell line, KPL-1, derived from a patient with recurrent disease which appeared under tamoxifenadministration. In a previous study, we suggested that this cell line is estrogen receptor (ER)-positive but tamoxifen-resistant. In the present study, the effects of a pure antiestrogen, ICI 182,780, on this cell line were investigated. Although tamoxifen inhibited neither cell growth nor estradiol-stimulated transcriptional activity in vitro, ICI 182,780, significantly inhibited both of them. Tamoxifen and ICI 182,780 were then administered to female nude mice bearing KPL-1 tumors. Tamoxifen had no effect on tumor growth, but ICI 182,780 unexpectedly stimulated it (p = 0.022). Estradiol tended to inhibit tumor growth (p = 0.198). Immunohistochemical analysis revealed that ICI 182,780 significantly increased the Ki6-labeling index (p<0.001) but estradiol decreased it (p = 0.035). To explore the possible mechanisms of these phenotypes, the mRNA levels of ER-alpha,ER-beta, transforming growth factor-beta1, fibroblast growth factor (FGF)-1 and FGF-4 in KPL-1 cells were compared with those in other ER-positive human breast cancer cell lines by reverse-transcription polymerase chain reaction. FGF-1 was overexpressed only in KPL-1 cells. This cell line is the first breast cancer cell line to be growth-stimulated by ICI 182,780 in vivo. Paracrine interaction between tumor cells and stromal cells mediated by growth factors, such as FGF-1, might be a key factor to explain the unique hormone responsiveness of KPL-1 cells.
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PMID:A pure antiestrogen, ICI 182,780, stimulates the growth of tamoxifen-resistant KPL-1 human breast cancer cells in vivo but not in vitro. 985 99

The human diet contains industrial-derived, endocrine-active chemicals and higher levels of naturally occurring compounds that modulate multiple endocrine pathways. Hazard and risk assessment of these mixtures is complicated by noadditive interactions between different endocrine-mediated responses. This study focused on estrogenic chemicals in the diet and compared the relative potencies or estrogen equivalents (EQs) of the daily consumption of xenoestrogenic organochlorine pesticides in food (2.44 micrograms/day) with the EQs in a single 200-ml glass of red cabernet wine. The reconstituted organochlorine mixture contained 1,1,1-trichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl)ethane, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, endosulfan-1, endosulfan-2, p,p'-methoxychlor, and toxaphene; the relative proportion of each chemical in the mixture resembled the composition reported in a recent U.S. Food and Drug Administration market basket survey. The following battery of in vitro 17 beta-estradiol (E2)-responsive bioassays were utilized in this study: competitive binding to mouse uterine estrogen receptor (ER); proliferation in T47D human breast cancer cells; luciferase (Luc) induction in human HepG2 cells transiently cotransfected with C3-Luc and the human ER, rat ER-alpha, or rat ER-beta; induction of chloramphenicol acetyltransferase (CAT) activity in MCF-7 human breast cancer cells transfected with E2-responsive cathepsin D-CAT or creatine kinase B-CAT plasmids. For these seven in vitro assays, the calculated EQs in extracts from 200 ml of red cabernet wine varied from 0.15 to 3.68 micrograms/day. In contrast, EQs for consumption of organochlorine pesticides (2.44 micrograms/day) varied from nondetectable to 1.24 ng/day. Based on results of the in vitro bioassays, organochlorine pesticides in food contribute minimally to dietary EQ intake.
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PMID:Comparative estrogenic activity of wine extracts and organochlorine pesticide residues in food. 986 Aug 91

To elucidate the mechanisms involved in anti-oestrogen resistance, two human breast cancer cell lines MCF-7 and the ICI 182780-resistant cell line, MCF-7/182R-6, have been compared with regard to oestrogen receptor (ER) expression, ER function, ER regulation, growth requirements and differentially expressed gene products. MCF-7/182R-6 cells express a reduced level of ER protein. The ER protein is functional with respect to binding of oestradiol and the anti-oestrogens tamoxifen, 4-hydroxy-tamoxifen and ICI 182780, whereas expression and oestrogen induction of the progesterone receptor is lost in MCF-7/182R-6 cells. The ER protein and the ER mRNA are regulated similarly in the two cell lines when subjected to treatment with oestradiol or ICI 182780. Oestradiol down-regulates ER mRNA and ER protein expression. ICI 182780 has no initial effect on ER mRNA expression whereas the ER protein level decreases rapidly in cells treated with ICI 182780, indicating a severely decreased stability of the ER protein when bound to ICI 182780. In vitro growth experiments revealed that the ICI 182780-resistant cell line had evolved to an oestradiol-independent phenotype, able to grow with close to maximal growth rate both in the absence of oestradiol and in the presence of ICI 182780. Comparison of gene expression between the two cell lines revealed relatively few differences, indicating that a limited number of changes is involved in the development of anti-oestrogen resistance. Identification of the differentially expressed gene products are currently in progress.
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PMID:Differential regulation of specific genes in MCF-7 and the ICI 182780-resistant cell line MCF-7/182R-6. 1002 3

Potential protective effects of the gonadal steroid estrogen on neurons are of particular interest in aging, neurodegenerative disease, and other traumatic conditions. In this study, we examined the hypothesis that estrogen, acting through the estrogen receptor (ERalpha), can enhance neuronal cell survival in the face of serious apoptotic challenge. PC12 cells were transfected with full-length rat ERalpha cDNA and a number of stable transfectants that expressed ER mRNA and protein (PCER cells) at levels comparable to those present in uterus or the MCF7 breast cancer cell line were obtained. A control line of cells transfected with vector DNA alone (PCCON cells) was used for comparisons. The apoptotic challenge used in the experiments was serum-free media, as it is well established that undifferentiated PC12 cells rapidly undergo cell death via apoptosis under those conditions. Estrogen treatment of PCER cells markedly increased the viability of these cells relative to PCCON cells in serum-free media, as assessed by trypan blue staining and TUNEL staining. We also examined the mitotic effects of estrogen treatment. While estrogen significantly stimulated bromodeoxy uridine (BrdU) incorporation into PCER cells in low-serum, but otherwise steroid-free media, no BrdU incorporation occurred in serum-free media. Mitotic effects of estrogen in low-serum steroid-free media were completely abolished by treatment with the estrogen receptor antagonist ICI 182,780. From this we conclude that the effects of estrogen on PCER cells in serum-free media can be attributed to increased cell survival, rather than proliferation.
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PMID:Stable transfection of PC12 cells with estrogen receptor (ERalpha): protective effects of estrogen on cell survival after serum deprivation. 1021 81

The progression of human breast cancer is often associated with a loss of estrogen dependence for growth, a resistance to estrogen antagonists such as tamoxifen, and the metastatic spread of the disease to secondary sites. Cell lines developed from such advanced breast tumors are often metastatic in athymic mice, show a loss of estrogen receptor mRNA and protein (ER-), and do not respond to 17beta-estradiol. However many advanced human breast tumors do express significant amounts of ER transcript, especially when analyzed by more sensitive methods of detection including RT-PCR and Ribonuclease Protection Assay (RPA). No metastatic, ER+breast tumor cell line has previously existed to examine the role of ER in metastatic progression and acquired drug (tamoxifen) resistance. The GI-101A cell line was recently developed from a metastatic breast tumor xenograft and is both tumorogenic and metastatic to the lungs and lymph node when injected into athymic mice, a pattern similar to that seen in patients. While Western blot analysis initially indicated that GI-101A was ER-, analysis of ER mRNA by RT-PCR and RPA have demonstrated the expression of ER (as well as EGF receptor and neu oncogene) transcripts. Functional ER in GI-101A was confirmed by a clear growth response to 17beta-estradiol in culture. Optimal 17beta-estradiol concentrations were significantly lower for GI101A than for MCF-7 (1 n m as opposed to >/=10 n m), and GI-101A growth was inhibited at 17beta-estradiol concentrations above 10 n m. Unlike MCF-7 cells, GI-101A shows constitutive expression of pS2 protein in hormone depleted media with no apparent induction by 17beta-estradiol supplimentation, as well as a resistance to the anti-estrogen tamoxifen at concentrations up to 10 n m. Finally, ER transcripts which likely represent an alternately spliced ER variant which has previously been shown to encode a constitutively active ER protein have been detected in GI-101A at levels similar to the wild type transcript, and offer a possible mechanism for estrogen independence, tamoxifen resistance, and constitutive pS2 expression.
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PMID:A metastatic breast tumor cell line, GI-101A, is estrogen receptor positive and responsive to estrogen but resistant to tamoxifen. 1032 49

Mutations of the breast cancer susceptibility gene BRCA1 confer increased risk for breast, ovarian, and prostatic cancers, but it is not clear why the mutations are associated with these particular tumor types. In transient transfection assays, BRCA1 was found to inhibit signaling by the ligand-activated estrogen receptor (ER-alpha) through the estrogen-responsive enhancer element and to block the transcriptional activation function AF-2 of ER-alpha. These results raise the possibility that wild-type BRCA1 suppresses estrogen-dependent transcriptional pathways related to mammary epithelial cell proliferation and that loss of this ability contributes to tumorigenesis.
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PMID:BRCA1 inhibition of estrogen receptor signaling in transfected cells. 1033 89


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