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

After nuclear translocation of estrogen receptors in MCF-7 human breast cancer cells, a processing takes place resulting in a 30-70% decline in the number of estradiol-binding sites measured in nuclear extracts. We have investigated the mechanism of estrogen receptor processing and obtained evidence that multiple events are involved. We confirm, as others have shown previously, that processing involves a decrease in the amount of estradiol binding in MCF-7 cells. In addition, evidence is provided for the generation of a rapidly dissociating population of estradiol-binding sites as an early event in processing. There is a single, slowly dissociating population of estrogen binding sites when MCF-7 cells are exposed to estradiol in the presence of actinomycin D, an inhibitor of receptor processing. One hour after the addition of sufficient estradiol to induce receptor processing, an additional, more rapidly dissociating population of estrogen binding sites is detected. When cells are exposed to estradiol and ethidium bromide, a drug which shares many actions with actinomycin D, but does not inhibit receptor processing, the rapidly dissociating population of estradiol-binding sites is again observed. Significantly, the loss of estradiol-binding sites from MCF-7 cells associated with processing between 1 and 6 h of estradiol exposure, occurs exclusively from the rapidly dissociating population of sites. Whole cell equilibrium-binding assays were performed with MCF-7 cells after 30 min or 5 h of estradiol exposure to determine whether the detected changes in estradiol dissociation reflected affinity changes in a subpopulation of estrogen-binding sites. Although the number of sites detected per cell varied with the assay method employed, binding to a single saturable class of higher affinity sites is always observed. High affinity estradiol-binding sites were reduced by 45% after a 5-h incubation with estradiol in both assay methods. The loss of estradiol binding during processing may therefore be explained by the conversion of certain high affinity estrogen receptors to a rapidly dissociating form which then fails to rebind hormone, or undergoes subsequent reactions that destroy hormone binding activity. Additionally, after 6 h of exposure to estradiol, the remaining receptor-bound estradiol dissociates from intact cells with a rate increased by 50% over that seen from the slow dissociating receptors present at 1 h.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Kinetic alterations in estrogen receptors associated with estrogen receptor processing in human breast cancer cells. 620 52

Some human tumors express known antigens that can be utilized as targets for specific immunotherapy. An absolute requirement for the efficacy of this therapeutic strategy is an adequate expression of the candidate antigen by all cells of the primary and metastatic tumor. To examine the presence and distribution of tumor-associated antigens in metastatic breast cancer, we used PCR analysis and ethidium bromide staining to test the expression of genes of the MAGE family in 28 primary tumors and related metastatic samples. Overall, samples obtained from 7 of 28 patients revealed positive. However, 2 of 3 primary tumors positive for MAGE-1 and/or MAGE-3 had corresponding negative metastatic lesions. On the contrary, 4 of the 25 MAGE-negative primary tumors gave rise to positive metastatic nodes. Our results confirm in vivo, at the molecular level, the tumor-antigen heterogeneity previously observed at the cellular level by in vitro analysis. Our data strongly suggest that, at least in patients with breast cancer, multiple different antigens would be required to optimize the recognition of neoplastic cells in immunotherapeutic protocols using MAGE products as target antigens.
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PMID:Expression of the MAGE gene family in primary and metastatic human breast cancer: implications for tumor antigen-specific immunotherapy. 762 12

A possible autocrine function of prolactin (Prl) in human breast cancer was explored by the addition of a panel of anti-human Prl mAbs to T47Dco and MCF7 human breast adenocarcinoma cells. mAb 631 and mAb 390 inhibited cell growth by 86 and 68%, respectively, in the estrogen receptor-negative T47Dco cells and by 20 and 71%, respectively, in the estrogen receptor-positive MCF7 cells. Conditioned medium prepared from T47Dco cells was assessed for the presence of Prl-like molecules by its ability to stimulate growth of Prl-responsive Nb2 rat lymphoma cells. Growth of Nb2 cells under the influence of human Prl or conditioned medium was abolished when either solution was pretreated with mAb 390, followed by Immunobead precipitation (Bio-Rad, Melville, NY). T47Dco cells secrete 0.7 microgram lactogen/ml over a 24-48-h period. With the use of reverse transcription-PCR, an expected 612-bp band was detected by ethidium bromide staining, and its similarity to pituitary Prl was confirmed by Southern blot analysis with the use of human Prl cDNA as a probe. A single M(r) 22,000 band, the dominant size of monomeric pituitary Prl, was found in immunoprecipitates of both cell extracts and conditioned medium from T47Dco cells labeled metabolically with [35S]cysteine. These data suggest that human breast cancer cells synthesize and secrete biologically active Prl.
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PMID:Prolactin synthesis and secretion by human breast cancer cells. 778 Sep 73

The synthesis of a 16 alpha-(bromoalkylamide) derivative of estradiol (N-butyl, N-methyl, 11-[3',17' beta-(dihydroxy)-1',3',5' (10')-estratrien-16' alpha-yl]-9(R/S)-bromo undecanamide) was performed by two different approaches starting from estrone. Each approach has the same key intermediate, containing an aldehyde group, but differs by the bromination step and the timing of formation of the amide group. This compound was found to cause, at 100 microM, a complete inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) responsible for the interconversion of estrone and estradiol. The corresponding IC50 value was 10.6 microM. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, this estradiol derivative has no estrogenic activity at 30 nM and only a minimal estrogenic activity (10% above the basal level) at 1 microM. At this latter concentration, this compound causes a 28% inhibition of 0.1 nM E2-induced cell proliferation (antiestrogenic activity). Thus, the introduction of a side-chain with a secondary bromide and a butyl methyl amide group at the 16 alpha-position of estradiol has two interesting effects; namely an inhibition of cytosolic 17 beta-HSD and a blockade of the estrogenic effect of estradiol.
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PMID:N-butyl, N-methyl, 11-[3',17' beta-(dihydroxy)-1',3',5'(10')-estratrien-16' alpha-yl]-9(R/S)-bromo undecanamide: synthesis and 17 beta-HSD inhibiting, estrogenic and antiestrogenic activities. 784 36

A simple spectrophotometric method for measuring DNA in proliferating cells is described. The method is an adaptation of the widely used diphenylamine (DPA) reaction to examine DNA in cells grown in a 96-well plate. This assay was capable of detecting as little as 10 ng DNA and could be used to measure DNA in stored as well as viable tissue samples. The DPA assay paralleled the MTT (3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay of mitochondrial reductase in A549 cells, a human lung cancer cell line; in EMT6 cells, a mouse breast cancer cell line; and in a primary cell culture of neonatal rat astrocytes. Over several days of proliferative growth in tissue culture, the ratio of MTT to DPA remained constant. Since the DPA assay and MTT assay measured different parameters of the same cells, they could be employed as complementary spectrophotometric assessments of cell growth on a 96-well plates using the same automated enzyme-linked immunosorbent assay plate reader.
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PMID:Adaptation of the diphenylamine (DPA) assay to a 96-well plate tissue culture format and comparison with the MTT assay. 794

Antisense oligonucleotides appear to offer considerable promise as sequence-specific inhibitors of gene expression. Different cellular targets for oligodeoxynucleotides with oncologic interest have been identified such as oncogenes, growth factors, and cell cycle-related genes. DNA polymerase alpha (pol alpha) plays a relevant role in DNA synthesis and cell proliferation. Pol alpha gene expression is constitutive throughout the cell cycle and its mRNA content and activity are related to the growth rate and neoplastic phenotype. The effects of a 18-mer pol alpha antisense oligomer on the proliferation of the MDA-MB 231 breast cancer cell line have been investigated. After 48 h in culture with oligomers (10 microM), about 50% growth inhibition was observed in antisense-treated cells, as evaluated by 3-(4,5-dimethythiazol-2yl)-2,5-diphenyltetrazolium bromide assay and cell count. [3H]Thymidine incorporation exhibited a 90% inhibition of DNA synthesis associated to 64% accumulation of cells at the G1-S border of the cycle as by flow cytometry, at 24 h. Northern hybridization and SDS-PAGE of immunoprecipitated MDA-MB 231 cell lysates revealed a decreased expression of pol alpha mRNA and a reduction of the 180-kDa polypeptide, respectively. Collectively, the data further confirm the relevance of pol alpha in the replicative cycle, as well as strengthen the potentiality of the antisense strategy for the control of gene expression and cell growth.
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PMID:Antiproliferative effect of DNA polymerase alpha antisense oligodeoxynucleotides on breast cancer cells. 850 May 51

Usefulness of MUC1 mRNA and keratin 19 mRNA as a target of reverse-transcriptase polymerase chain reaction (RT-PCR) was compared in the detection of breast cancer micrometastases in axillary lymph nodes. RT-PCR amplification of MUC1 mRNA and keratin 19 mRNA was conducted using total RNA samples. RT-PCR products were stained with ethidium bromide and analyzed by agarose gel electrophoresis. Expression of both MUC1 mRNA and keratin 19 mRNA was detected by RT-PCR in a breast cancer cell line (MRK) and in all the 23 primary breast cancers but not in the control lymph nodes obtained from patients with benign diseases. A serial dilution study of MRK cells against normal lymph node cells has shown that detection sensitivity of MUC1 RT-PCR and keratin 19 RT-PCR were 1/10(5) and 1/10(6) (cancer/lymph node cells), respectively. Sixty-three axillary lymph nodes were obtained from 23 patients with primary breast cancer, and metastases in each lymph node were investigated by histological examination (hematoxylin and eosin sections) and RT-PCR method. In all 10 lymph nodes, which were histologically metastasis-positive, both MUC1 mRNA and keratin mRNA were detected by RT-PCR. Of the 53 histologically negative lymph nodes, 3 (6%) and 5 (9%) lymph nodes were found to express MUC1 mRNA and keratin 19 mRNA, respectively, indicating the presence of micrometastases which could be detected by RT-PCR but not by histological examination. These results demonstrate the usefulness of both MUC1 RT-PCR and keratin 19 RT-PCR in the detection of breast cancer micrometastases in lymph nodes, and also indicate the superiority of keratin 19 RT-PCR over MUC1 RT-PCR because of its higher detection sensitivity.
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PMID:Detection of breast cancer micrometastases in axillary lymph nodes by means of reverse transcriptase-polymerase chain reaction. Comparison between MUC1 mRNA and keratin 19 mRNA amplification. 857 27

The schedule-dependent interaction of paclitaxel and cisplatin was studied in four human carcinoma cell lines: non-small cell lung cancer, A549; breast cancer, MCF7; ovarian cancer, PA1; and colon cancer, WiDr cells. The cells were exposed simultaneously to the drugs for 24 h and sequentially to paclitaxel first for 24 h followed by cisplatin for 24 h, or vice versa, and then incubated in drug-free medium for 4 and 3 days, respectively. Cell growth inhibition was then determined by the 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of drug combinations at the IC80 level were analyzed by the isobologram method. On simultaneous exposure to paclitaxel and cisplatin, additive and subadditive (slight antagonistic) effects were observed in A549, MCF7, and PA1 cells, while sub-additive and protective (antagonistic) effects were observed in WiDr cells. On sequential exposure to paclitaxel first, followed by cisplatin, additive effects were observed in all cell lines. On sequential exposure to cisplatin first, followed by paclitaxel, additive effects were observed in PA1 cells, while additive, sub-additive, and protective effects were observed in A549, MCF7, and WiDr cells. These findings suggest that the interaction of paclitaxel and cisplatin is schedule- and cell line-dependent. The optimal schedule of this combination may be paclitaxel first followed by cisplatin.
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PMID:In vitro schedule-dependent interaction between paclitaxel and cisplatin in human carcinoma cell lines. 861 5

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.
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PMID:Human astrocytoma cells express a unique chloride current. 874 85

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.
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PMID:Human astrocytoma cells express a unique chloride current. 880 32


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