Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative expression in human breast cancer cells of messenger ribonucleic acids (mRNA) encoding different steroid hormone receptors is unknown. Accordingly, mRNA levels in total RNA extracted from 13 human breast cancer cell lines were measured by Northern analysis employing complementary DNA probes for the human oestrogen (ER), progesterone (PR), androgen (AR), vitamin D3 (VDR) and glucocorticoid receptors (GR). The 7 ER+ lines expressed a single 6.4 kilobases (kb) ER mRNA. Interestingly, low concentrations of ER mRNA were detected in the ER- cell lines, MDA-MB-330 and BT 20. PR mRNA, predominantly a 13.5 kb species, was expressed in the 6 lines known to be ER+, PR+ by radioligand binding; however, one ER+ cell line, MDA-MB-134, failed to express PR mRNA. A 10.5 kb AR mRNA was expressed at significantly higher levels in ER+ than ER- cell lines. All cell lines expressed a single 4.6 kb mRNA for VDR and a single 7.4 kb mRNA for GR. ER and PR mRNA levels were positively correlated (p = 0.011) and each was positively correlated with androgen receptor (AR) mRNA levels (p less than or equal to 0.009). ER, PR and AR mRNAs were negatively associated with GR levels (p less than or equal to 0.012), while ER and AR mRNA levels were negatively correlated with mRNA for the epidermal growth factor receptor. In contrast, levels of VDR mRNA were unrelated to the concentration of any other steroid receptor mRNA. Our data demonstrate the coordinate expression of ER, PR and AR genes, and an inverse relationship between sex steroid hormone receptor and GR gene expression in human breast cancer cell lines.
 ...
PMID:Steroid hormone receptor gene expression in human breast cancer cells: inverse relationship between oestrogen and glucocorticoid receptor messenger RNA levels. 224 95

Experimentally, a portion of the detectable cellular estrogen receptor (ER) is seen to disappear in human breast cancer cells submitted to estradiol treatment. In this study, we have applied several detection methods to analyze the loss (processing) then the replenishment of ER in the MCF-7 cell line. Radioligand exchange assay and enzyme immunoassay revealed an accumulation of ER in the nuclei with a concomitant depletion in cytosol shortly after the addition of estradiol in cell culture. Then, a time-dependent decrease of ER level in the nuclear compartment without rescue in the cytosol was observed. When an immunocytochemical assay was performed on whole cells treated with estradiol, a similar decrease of ER number was shown, indicating that a decrease in the extractability of estradiol-filled ER was not involved in the processing. Analysis of ER mRNA also indicated that the estrogen treatment induces a time-dependent decrease of its expression. Measurement of [35S]methionine-labeled ER following the arrest of the hormone treatment suggested that ER replenishment was due to newly synthesized receptors. Sucrose gradient experiments confirmed the generation of small molecular forms of ER, following its binding with estradiol. All these data are indicative of estrogen-receptor complex degradation. We also confirm that estrogen regulates ER level through the decrease of its mRNA expression.
 ...
PMID:Expression of estrogen receptor and its messenger ribonucleic acid in the MCF-7 cell line: multiparametric analysis of its processing and regulation by estrogen. 228 76

Poly A+ RNA isolated from the human breast cancer cell line MCF-7 was fractionated by sucrose gradient centrifugation and those fractions enriched in oestrogen receptor (ER) mRNA were used to prepare randomly primed cDNA libraries in the lambda gt11 vectors. Clones corresponding to the ER were isolated from both libraries after screening with either ER monoclonal antibodies (lambda gt11) or synthetic oligonucleotide probes designed from two peptide sequences of purified ER (lambda gt10). Five cDNA clones were isolated by antibody screening and five after screening with synthetic oligonucleotides. The two largest ER cDNA clones, lambda OR3 (1.3 kbase) and lambda OR8 (2.1 kbase), isolated using antibodies and oligonucleotides, respectively, were able to enrich selectively for ER mRNA by hybrid-selection. Furthermore, lambda OR8 contains DNA sequences which cross-hybridize with each of the other ER cDNA clones. These results demonstrate that the clones isolated correspond to the ER mRNA sequence. Using lambda OR8 as a hybridization probe revealed a single poly A+ RNA band of approx. 6.2 kbase in the ER containing human breast cancer cell lines MCF-7 and T47D. In contrast, no hybridization was seen in the human ER-cell line HeLa. The same probe hybridizes to a chicken gene which is expressed in oviduct tissue as a 7.5 kbase poly A+ RNA.
 ...
PMID:Cloning of the human oestrogen receptor cDNA. 242 49

We have previously demonstrated that regulation of estrogen receptor (ER) expression in MCF-7 breast cancer cells is a complex process involving transcriptional and posttranscriptional regulation by estradiol. Treatment of MCF-7 cells with estradiol results in the down-regulation of receptor expression; posttranscriptional suppression of receptor mRNA appears to be the predominant mechanism. To determine whether posttranscriptional regulation of ER gene expression is mediated by an ER-dependent mechanism independent of protein synthesis, we have used the competitive estrogen antagonist, 4-hydroxytamoxifen, and the inhibitor of protein synthesis, cycloheximide, to study regulation of ER mRNA by estradiol. 4-Hydroxytamoxifen had no effect on the steady-state level of receptor mRNA and effectively blocked the suppression of ER mRNA by estradiol. The metabolic inhibitor, cycloheximide, was unable to prevent the estrogen induced decrease in ER mRNA. These data provide evidence that the posttranscriptional suppression of ER expression through estradiol is mediated through the ER independent of protein synthesis. A study of the effects of estradiol on the steady-state levels of nuclear and cytoplasmic receptor mRNA suggest that posttranscriptional suppression is a nuclear event.
 ...
PMID:Role of an estrogen receptor-dependent mechanism in the regulation of estrogen receptor mRNA in MCF-7 cells. 260 58

The effects of short- and long-term estrogen deprivation on T47D human breast cancer cells was studied. Cells were routinely grown in an estrogenized environment in media containing fetal bovine serum with phenol red indicator. Cells were estrogen deprived (grown in media containing dextran-coated charcoal-stripped fetal bovine serum without phenol red) for either 10 days or at least 8 months, and effects on genotype, receptor content, and cell growth responsiveness were studied. Cells grown in an estrogenized environment are hypertetraploid, whereas long-term estrogen-deprived cells have become hyperdiploid. Short-term estrogen-deprived cells exhibit a decreased growth rate and progesterone receptor (PgR) content, while estrogen receptor (ER) content is not significantly altered. ER mRNA levels are significantly decreased in these cells. Incubation of these cells with estradiol (10(-10) M) for 6 days causes a 5-fold stimulation in cell growth and this stimulation can be inhibited by the antiestrogens 4-hydroxytamoxifen (4-OHT), ICI 164,384, and RU 39411. Cells cultured under long-term estrogen deprivation exhibited an increased growth rate and were refractory to the effects of estradiol and of 4-OHT on cell growth. These cells were ER negative with low levels of PgR; however, one clone of this line was found to be ER and PgR negative. No mRNA for the ER was detected in this line or its clone. With these cell lines it is possible to study the biological characteristics necessary for the outgrowth of a receptor negative, hormone nonresponsive cell population from a receptor positive, hormone-responsive population grown in a estrogen-free environment.
 ...
PMID:Short- and long-term estrogen deprivation of T47D human breast cancer cells in culture. 263 59

The estrogen receptor (ER) is present in a wide variety of mammalian tissues and is required for physiological estrogen responses, including estrogen-induced tissue-specific changes in gene expression. We studied the estrogen regulation of the mRNAs encoding the ER in rat uterus, liver, and pituitary. Ovariectomized (21-28 day post surgery) female CD-1 rats were injected daily with 17 beta-estradiol (E2, 10 micrograms/100 g BW) for 0, 1, or 4 h, 1, 3, or 7 days and compared with intact controls. Steady-state levels of ER mRNA were quantified using a human ER cDNA probe. Only one hybridizing species of approximately 6.2 kilobase (kb) was detected in uterine and liver RNA, similar to that observed in MCF7 human breast cancer cells. However, the ER mRNA regulation by E2 differed in direction depending on the tissue examined. In uterus, ER mRNA increased 3- to 6-fold after ovariectomy, and returned to intact levels within 24 h of E2 replacement. In contrast, liver ER mRNA declined 1.5- to 3-fold after ovariectomy and returned to intact levels after 1-3 days of E2. In pituitary tissue two hybridizing forms of ER mRNA were observed, with one species migrating at 6.2 kb, equivalent to the form in other tissues, and a second smaller species at approximately 5.5 kb. The lower molecular weight species varied somewhat in abundance from animal to animal, averaging about 20% of the intensity of the 6.2 kb band. The ER mRNA forms were regulated positively with E2.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tissue-specific regulation of rat estrogen receptor mRNAs. 272 29

Previous studies have demonstrated an inverse relationship between estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in human breast cancer cells. This relationship was further investigated in MCF 7 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Exposure to 10 nM TPA resulted in a time-dependent increase in EGF-R mRNA, first apparent at 3 h and maximal between 9 and 24 h. There was a concomitant fall in ER mRNA with a maximum decline to 15-20% of control between 12 and 24 h. Although EGF-R mRNA levels declined between 24 and 72 h, both EGF-R mRNA and EGF-R binding remained above control levels and this was accompanied by a sustained depression of ER mRNA. These data support the view that ER and EGR-R gene expression is inversely regulated in human breast cancer and describe for the first time an inhibitory effect of a phorbol ester on steroid hormone receptor gene expression.
 ...
PMID:Modulation of estrogen receptor and epidermal growth factor receptor mRNAs by phorbol ester in MCF 7 breast cancer cells. 275 60

Since sex steroid hormones and growth factors are known to modulate the proliferation of breast tumors, we have studied the effects of estrogen and progestin, their antagonists, and growth factors on the regulation of estrogen receptor (ER) mRNA and protein levels in T47D breast cancer cells, which contain low levels of ER, and in two sublines of MCF-7 cells which contain high ER levels. The mRNA levels were measured by Northern blot analysis using lambda OR8, a cDNA probe for ER, and protein levels were measured by hormone binding or Western blot analysis. Treatment of T47D cells with estradiol (E2) caused a 2.5-fold increase in ER mRNA (6.6 kilobases) levels after 48 h. The progestin R5020 evoked a marked decrease in ER mRNA and protein levels to 20% of control values, while the antiprogestin RU38,486 caused no change in ER. In MCF-7 cells, the effect of E2 on ER levels was dependent on the prior growth history of the cells. In cells grown in low estrogen [5% charcoal-dextran-treated calf serum with phenol red for 8 yr (MCF-7-K2)], which are still E2 responsive, treatment with E2, the antiestrogen LY117018, or both produced little change in ER mRNA or protein; in contrast, ER mRNA and protein were reduced by E2 to 40% and 50% of control levels, respectively, in MCF-7 cells (denoted MCF-7-K1) which had been maintained routinely in medium containing 5% calf serum. This decrease in ER mRNA was dose dependent; 10(-11) E2 reduced levels to 60%, and 10(-10) M E2 evoked the maximal drop to 40% of the control level in 2 days. LY117018 alone did not alter ER mRNA levels in these cells, but it completely prevented the down-regulation of ER by E2. Administration of progestin, but not antiprogestin, along with E2 partially prevented the decrease in ER evoked by E2. Addition of epidermal growth factor or insulin-like growth factor-I to MCF-7-K1 cells, which increased cell proliferation, had no detectable effect on ER levels. Treatment with transforming growth factor-beta, which decreased cell proliferation, reduced ER by about 20%.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of estrogen receptor messenger ribonucleic acid and protein levels in human breast cancer cell lines by sex steroid hormones, their antagonists, and growth factors. 278 42

Using a combination of hormone-binding assays, immunologic techniques, and mRNA hybridizations we have measured the estrogen receptor (ER) content and studied the hormonal regulation of ER mRNA in one estrogen responsive and one estrogen unresponsive breast cancer cell line, MCF-7 and T47Dco, respectively. Estradiol binding could be detected in cytosol from MCF-7 cells but not in T47Dco cells. However, when measured by an enzyme-linked immunosorbent assay, T47Dco cells were found to contain approximately 15 fmol ER/mg cytosolic protein or 10% of the ER content in MCF-7 cells. Immunologically reactive ER in T47Dco cells was indistinguishable in size (approximately equal to 68 KD) from the ER in MCF-7 cells, as shown by Western blotting using a monoclonal antihuman ER antibody. Quantification of ER mRNA in MCF-7 and T47Dco cells indicated that T47Dco cells contained approximately 50% of the ER mRNA levels found in MCF-7 cells. This basal level of ER mRNA in T47Dco cells was not decreased by estradiol treatment, as opposed to in MCF-7 cells where estradiol caused 40-60% decrease in the ER mRNA expression. Also, estradiol did not increase the progesterone receptor (PR) mRNA levels in T47Dco cells whereas in MCF-7 cells an approximately 5-fold increase of the PR mRNA levels occurred after estradiol treatment. However, incubation of the cells with the synthetic progestin R5020 decreased the ER mRNA levels to approximately the same degree in both cell lines. In conclusion, we have shown that estrogen down-regulates ER mRNA and up-regulates PR mRNA in MCF-7 cells. Neither of these estrogenic effects were seen in T47Dco cells. It appears that the steroid-resistance in T47Dco cells does not occur as a consequence of a complete absence of ER mRNA or protein.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hormonal regulation of estrogen receptor messenger ribonucleic acid in T47Dco and MCF-7 breast cancer cells. 291 47

The influence of oral high-dose (HD) medroxyprogesterone acetate (MPA) and megestrol acetate (MA) treatment on steroid hormone receptor levels in metastatic breast tumor tissue was investigated. In ten postmenopausal women with advanced breast cancer, receptor biopsies were obtained from the same tumor before the start, and one and eight weeks after the start of oral HD progestin treatment. Endocrine treatment had been stopped in all patients at least five weeks before the start of progestin treatment. Estradiol receptor (ER) levels were reduced by 26.9% and 20.0% respectively after one and eight weeks of treatment. Progesterone receptors (PgR) were significantly reduced to undetectable levels, possibly due to MPA and MA binding to PgR. A stepwise decrease in androgen receptors (AR) was observed, indicating that the two progestins (MPA and MA) may also act through AR, and/or interfere with the replenishment of AR.
 ...
PMID:The influence of progestins on receptor levels in breast cancer metastasis. 303 71


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>