Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to determine whether the hepatocyte growth factor/scatter factor (HGF/SF)- and keratinocyte growth factor-receptor systems were expressed in normal breast cells, breast carcinoma cell lines, normal breast tissues, and breast cancer tissues. Reverse transcriptase-polymerase chain reaction and hot blotting were used to detect HGF, HGF/SF (met) receptor, KGF, and KGF receptor mRNAs in human mammary epithelial (HME) and stromal (HMS) cells. We also examined breast carcinoma (MDA-MB-157, SCC 38, and SCC 70) and spontaneously immortalized breast epithelial (HMT 3522) cell lines, as well as normal breast and breast carcinoma tissues. PCR products were also confirmed by nucleic acid sequencing. The effects of HGF and KGF, compared to EGF and heparin-binding EGF, on the proliferation of normal human mammary epithelial cells in serum-free defined medium was determined by cell counting. HGF and KGF mRNAs were detected in HMS cells, but not HME cells. KGF receptor mRNA was detected in HME cells, but not HMS cells. HGF/SF receptor mRNA was detected in both HME and HMS cells. mRNAs were also detected in normal breast and breast carcinoma tissues, as well as breast carcinoma and transformed breast epithelial cell lines. Alternative cDNA sequences that are predicted to code for a soluble KGF receptor and a membrane bound, truncated HGF/SF receptor were detected in breast epithelial cells and breast tissues. HGF and KGF maintained viability and stimulated proliferation of HME cells.
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PMID:Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. 786 34

The recent demonstration that bone sialoprotein (BSP) can be detected in human breast cancer tissue by immunoperoxidase suggests that this phosphoprotein is ectopically expressed by malignant mammary epithelial cells. Its detection in human breast cancer cells raises questions about its potential role(s) during breast cancer progression. Because BSP is secreted and is present in the serum, the positivity of breast cancer cells for BSP could have been the result of an uptake of the circulating phosphoprotein by the cells rather than of an intrinsic expression. We examined the expression of BSP at both the protein and mRNA levels in nine human breast cancer samples as well as in three human breast cancer cell lines (MCF-7, T47-D, and MDA-MB-231) using immunohistochemistry, flow cytometric analysis, immunoblot, and reverse-transcriptase PCR. BSP was detected at both protein and mRNA levels in human breast cancer tissue and in the three human breast cancer cell lines. Using a specific polyclonal anti-BSP antibody, we showed by both fluorescence-activated cell sorter analysis and immunohistochemistry experiments that all of the human breast cancer cell lines studied express BSP. This was localized at the cell surface and in the cytosol of the estrogen receptor-positive MCF-7 and T47-D cell lines, whereas it was detected only in the cytosol of the estrogen receptor-negative MDA-MB-231 cells. Using the same polyclonal anti-BSP antibody, we were able to identify an approximately 97-kd band on total protein extracts from the three cell lines by immunoblotting. Reverse-transcriptase PCR reactions using specific oligonucleotides performed on total RNA of nine human breast cancer biopsy samples and the three cell lines demonstrated the presence of BSP mRNA in all of the samples examined. This study is the first demonstration that human malignant breast epithelial cell lines express BSP at the protein and mRNA levels. Our study identified MCF-7, T47-D, and MDA-MB-231 cells as useful models for the examination of the molecular mechanisms involved in the ectopic expression of BSP in breast malignant lesions.
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PMID:Detection of bone sialoprotein in human breast cancer tissue and cell lines at both protein and messenger ribonucleic acid levels. 876 20

Sex hormone binding globulin (SHBG) is a high affinity binding protein for estrogens and androgens. SHBG has been found in breast tissue and cell lines through immunostaining. The goal of this series of experiments was to determine whether mRNA for SHBG is expressed in breast cancer cell lines and tumor tissue. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect SHBG and beta-2 microglobulin (control for tissue extractions). Three breast cancer cell lines, ZR-75-1, MCF-7, and MDA-MB-231 and 56 breast tissue samples were collected and analysed for SHBG mRNA expression. mRNA was successfully extracted from 30 of these breast tissue samples. SHBG mRNA was detected in ZR-75-1, MCF-7 and MDA-MB-231 cells, and in 11 of the breast tissue samples. Two PCR products were routinely amplified from the breast cancer cell line RNA, one at approximately 500 bp and another at approximately 300 bp. The DNA sequence of the 300 bp PCR produce was consistent with alternate splicing of the SHBG mRNA, where exon 7 is deleted, and is accompanied by a point deletion at the beginning of exon 8. SHBG protein production from the three breast cancer cell lines was detected by immunoprecipitation using an affinity purified SHBG antibody. SHBG mRNA was found in 11 of 30 samples of breast tissue. Some samples expressed only the 500 bp or the 300 bp PCR product, whereas others expressed both PCR products. The presence of SHBG mRNA in these samples was not associated with either the presence or absence of steroid receptors. SHBG mRNA is thus expressed in breast cancer cell lines, and in some breast tissue samples.
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PMID:Sex hormone binding globulin mRNA in human breast cancer: detection in cell lines and tumor samples. 901 Mar 21

We have investigated the mechanisms by which radiation inhibits proliferation of human breast cancer cells in culture. Radiation, within the dose range used for treatment of humans, decreased the rate of proliferation of estrogen-independent MDA-MB-231 cells more effectively than it did that of estrogen-dependent MCF-7 cells. The rate of proliferation of MDA-MB-231 cells was also inhibited to a greater extent than that of MCF-7 cells by purified TGFB1. Using an ELISA specific for activated TGFB1, we found that conditioned medium from irradiated MDA-MB-231 or MCF-7 cells contained twofold more TGFB1 than that from nonirradiated cells. Conditioned medium from irradiated breast cancer cells, but not from nonirradiated cells, inhibited the growth of untreated MDA-MB-231 cells. The inhibitory activity was blocked by an anti-TGFB1 neutralizing antibody. An approximately twofold increase in the TGFB1 mRNA in irradiated cells compared to controls was found using semiquantitative reverse-transcriptase PCR. Last, the mRNA for insulin-like growth factor binding protein 3, a reported target of the cell inhibitory activity of TGFB1, was increased threefold upon irradiation. Our results demonstrate that the TGFB1 is increased after irradiation and that the activation of the TGFB1 signaling pathway may sensitize cells to the effects of radiation.
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PMID:Regulation of transforming growth factor beta1 by radiation in cells of two human breast cancer cell lines. 1052 25

Metastasis is the process by which tumor cells spread from their site of origin to distant sites after gaining access to the circulatory system. An understanding of the factors contributing to the metastatic potential of breast cancer cells to bone will enhance the prospect of developing new therapies that impede metastasis. In this study, we have used an in vivo selection scheme involving left cardiac ventricle injection into nude mice to identify a highly metastatic human breast cancer cell line (MDA-MET) from a less metastatic (MDA-231) parental cell line. In this model, tumor-bearing mice exhibit features similar to those associated with human metastatic bone disease such as osteolytic bone destruction. After inoculation, MDA-MET cells form devastating lesions within 4 weeks, whereas the parental cells do not, even after 10 weeks. In vitro, the MDA-MET cells have a similar growth rate to the parental MDA-231 cells yet demonstrate distinct adhesive and invasive phenotypes. MDA-MET cells show increased early adhesion to type IV collagen and are significantly more invasive through Matrigel than MDA-231 cells. Analysis of the gene expression profile in the metastatic MDA-MET versus poorly metastatic MDA-231 cells identified relatively few genes whose expression was altered >2-fold. Of particular interest was the lack of parathyroid hormone-related protein (PTHrP) mRNA expression, which was supported at the protein level by immunoradiometric assay. These data support the idea that PTHrP is not predictive of the metastasis of human breast cancer to bone. Another important difference between the two cell lines was the elevated expression by MDA-MET cells of the cytokine IL-8. Reverse transcriptase-PCR and ELISA confirmed the increased expression of IL-8 in MDA-MET cells. In addition, IL-8 mRNA expression is also elevated in a variety of human cancer cell lines with different metastatic potential in vivo. These experiments suggest that the elevated expression of IL-8 (and not PTHrP) by MDA-MET cells is a phenotypic change that may be related to their enhanced ability to metastasize to the skeleton.
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PMID:Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. 1235 70

Autotaxin (ATX), originally isolated from human melanoma cells, is a novel metastasis-enhancing motogen and angiogenesis factor. In the present study, we compared the expression level of ATX mRNA between normal and breast cancer tissues and found that the expression of ATX mRNA was closely linked to invasiveness of cancer cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical analysis showed higher cellular ATX mRNA expression in the cancer than normal breast tissues. MDA-MB-435S breast cancer cells, expressing higher amount of ATX mRNA, showed greater relative invasiveness to fibroblast-conditioned medium (FCM) than MCF7, MDA-MB-231, and HBL-100 breast cancer cells. Furthermore, ATX-transfected MCF7 cells showed increased motility and invasiveness than vector-transfected MCF7 cells. Collectively, our results suggest that the expression of ATX is closely linked to the invasiveness of breast cancer cells.
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PMID:Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells. 1249 89

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and angiogenic growth factor that enhances endothelial cell invasion through the extracellular matrix (ECM). While various cell types express VEGF receptors, little is known about the biological actions of VEGF on nonendothelial cells. Therefore, the main objective of the present study was to determine the effect of VEGF on the in vitro invasiveness and proliferation of human MDA-MB-231 breast carcinoma cells and human HTR-8/SVneo trophoblast cells. Reverse-transcriptase polymerase chain reaction analysis demonstrated the presence of transcripts encoding VEGF receptors (VEGFR) -1, -2, and -3 as well as neuropilins-1 and -2 in the trophoblast cells, and the presence of transcripts encoding VEGFR-2 and neuropilins-1 and -2 in the breast carcinoma cells. Both cell lines also expressed transcripts for VEGF-A, -B, -C and -D, as well as for placenta growth factor (PlGF). Although incubation with exogenous VEGF-A(165) or VEGF-A(121) did not affect the rate of proliferation of either the trophoblast or the breast carcinoma cells, incubation with these molecules reduced their ability to invade through reconstituted ECM (Matrigel). The effect of VEGF-A(165) on the invasiveness of both cell lines was inhibited by the inclusion of a neutralizing antibody to VEGF. Exogenous VEGF-A(165) also decreased the cell surface expression of the urokinase-type plasminogen activator (a molecule required for invasion) by the breast carcinoma and trophoblast cells. These results indicate that the biological actions of VEGF on certain cell types may differ from the effects of this molecule on vascular endothelial cells, and therefore are relevant to angiogenesis-based therapies.
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PMID:Inhibition of breast carcinoma and trophoblast cell invasiveness by vascular endothelial growth factor. 1258 44

Characteristic behaviors of head and neck squamous cell carcinoma (HNSCC) include a propensity to occur as multiple synchronous and metachronous tumors, frequent recurrence and metastasis. Early detection of HNSCC and monitoring its recurrence are necessary to improve prognosis. Hyaluronic acid (HA), a component of extracellular matrix, promotes metastasis. Small fragments of HA stimulate angiogenesis. HA fragments are generated when hyaluronidase (HAase), an endoglycosidase, degrades the HA polymer. Using the HA test (an ELISA-like assay) we found that saliva HA levels are 4.9-fold elevated in 11 HNSCC patients (2841 +/- 887 ng/mg protein) when compared to 6 normal controls (579.3 +/- 122.6 ng/mg protein; p = 0.00238). HNSCC patients included in our study were patients with cancers of the oral cavity (n = 4), pharynx (n = 7) and larynx (n = 1). The HA levels were also elevated in MDA-1483, FaDu and HEp-2 cell lines when compared to the transformed keratinocyte line HEK-001. Saliva HAase levels measured using the HAase test (an ELISA-like assay) were 3.7-fold elevated in HNSCC patients (10.4 +/- 1.4 mU/mg protein) when compared to normal controls (2.8 +/- 0.7 mU/mg protein; p = 0.0028). MDA-1483 and HEp-2 cells secreted 7- to 11-fold higher levels of HAase in their conditioned media (CM) when compared to FaDu cells, and the latter secreted 1.5-fold more HAase than HEK-001 cells. Reverse transcriptase (RT)-PCR analysis detected the expression of full-length HYAL1 type HAase transcript in tumor cells. None of the cells exhibited the expression of PH20 in RT-PCR analysis. Immunoblot analysis confirmed the expression of a approximately 55 kDa HYAL-related protein in tumor cell CM and in patients' saliva. The pH activity profile and optimum (pH 4.4) of the HAase activity present in HNSCC patients' or normal saliva and that secreted in the CM of tumor cells closely resembled that of the partially purified HYAL1 type HAase. The profiles of HA species in HNSCC patients' and normal saliva are different. The high-stage HNSCC patients' saliva contains a high-molecular-mass HA species and HA fragments, in addition to the HA species present in the normal individual's saliva. These results show that HYAL1 is the major tumor-derived HAase expressed in HNSCC. Furthermore, HA and HAase may be sensitive and specific markers for detecting HNSCC and monitoring its recurrence. Further studies are needed to confirm these preliminary studies.
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PMID:Expression of tumor markers hyaluronic acid and hyaluronidase (HYAL1) in head and neck tumors. 1499 92

In this study we determined the activity of extracts from Bangladeshi medicinal plants (Emblica officinalis, Aegle marmelos, Vernonia anthelmintica, Oroxylum indicum, Argemone mexicana) on human breast tumor cell lines. Extracts from E. officinalis and O. indicum displayed anti-proliferative activity on MCF7 and MDA-MB-231 breast cancer cell lines, while extracts from A. mexicana were active on MCF7 cells, exhibiting on the contrary low antiproliferative effects on MDA-MB-231 cells. Extracts from A. marmelos and V. anthelmintica were antiproliferative on both cell lines, but at higher concentrations. The accumulation of estrogen receptor alpha (ERalpha) mRNA, a marker of neoplastic status, was analysed by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The data obtained demonstrated that only extracts from E. officinalis induce an increase of ERalpha mRNA in MCF7 cells. When MDA-MB-231 cell line was employed, extracts from E. officinalis, V. anthelmintica and A. mexicana were found to be inducers of the increase of ERalpha mRNA accumulation. Since activation of ERalpha gene expression could have clinical impact, our results suggest a possible use of extracts from medicinal plants to identify compounds of possible interest in the treatment of breast cancer.
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PMID:Effects of extracts from Bangladeshi medicinal plants on in vitro proliferation of human breast cancer cell lines and expression of estrogen receptor alpha gene. 1471 19

Progression of breast cancer implicates the degradation of extracellular matrix (ECM) by metallo-proteinases (MMPs), a process with important consequences on the growth and invasiveness of cancer cells in adjacent and distant sites. The isoflavone, genistein--a natural inhibitor of protein tyrosine kinase pathway--inhibits the growth of a wide range of cancer cells in vitro. The aim of this study was to investigate: i) the expression of mRNAs encoded for MMPs and their endogenous inhibitors (TIMPs) associated with pathogenesis and metastatic potential of breast cancer cells; and ii) the effect of genistein on the transcription of MMPs and TIMPs and the invasive potential of breast cancer cells. Gene expression at transcriptional level was examined in cell cultures of two epithelial breast cancer cell lines, the high invasive (ER-negative) MDA-MB-231 and the low invasive (ER-positive) MCF-7, as well as the normal mammary cells (MCF-12A) following RNA isolation and reversed transcriptase polymerase chain reaction (RT-PCR). The inhibitory effect of genistein on functional invasiveness was examined by a cell invasion assay. Cell cycle distribution showed that genistein arrested breast cancer MDA-MB-231, MCF-7 and BT-20 cells in the G2/M phase. Both normal and breast cancer cell lines express the genes of MMP-2, -9, MT1-, MT2-, MT3-MMP and TIMP-1, -2 and -3. MCF-7 express notably less MMPs than MDA-MB-231 cell line. The addition of genistein resulted in down-regulation of the transcription of all MMP genes in MDA-MB-231 and most of MMPs in MCF-7 cells. The inhibitory effect of genistein on MMPs was functionally confirmed, since it significantly reduced the invasion properties of cancer cells in vitro. The obtained results indicate that genistein may be of great value in prevention of breast cancer cell metastasis, since it represents both a transcriptional modulator of genes involved in this pathogenetic process and a suppressor of breast cancer cell invasiveness.
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PMID:Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors. 1575 8


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