Abstract：
:Aromatase plays a critical role in breast cancer development by converting androgen to estrogen. In this report, results are presented to demonstrate that estrogen, the product of aromatase, can up-regulate its expression. Estrogen receptor (ER) transient transfection experiments were performed using the SK-BR-3 breast cancer cell line, which is ER negative and expresses aromatase. When SK-BR-3 cells were transfected with the expression plasmid pCI-ER alpha, but not pCI-ER beta, aromatase activity was elevated by 17beta-estradiol (E(2)) in a dose-dependent manner. The E(2) induction could be enhanced by cotransfection with the coactivator GRIP1 and suppressed by antiestrogens such as tamoxifen and ICI 182,780. The aromatase activity in the ER alpha-transfected SK-BR-3 cells could also be induced by environmental chemicals that were known to have an estrogen-like activity. Using aromatase gene exon Is-specific reverse transcription-PCR, the level of promoter I.1-driven transcripts was found to be elevated in E(2)-treated ER alpha-transfected cells. This suggested that E(2) induced aromatase expression through the up-regulation of promoter I.1. Using DNA deletion analysis of the 5'-flanking region of promoter I.1, the section between -300 and -280 bp upstream from exon I.1 was identified to be important for mediating E(2) induction. However, a direct binding of ER alpha to this 20-bp region could not be demonstrated. It was found that E(2) induction could be suppressed by the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor, PD98059, and the epidermal growth factor receptor tyrosine kinase inhibitor, PD153035 hydrochloride. A significant induction of aromatase expression was also detected in ER-positive MCF-7 breast cancer cells after transfection with pCI-ER alpha and E(2) treatment. Furthermore, after ER alpha transfection and E(2) treatment, the aromatase activity in Her-2-overexpressing MCF-7 cells was drastically higher than that of the wild-type MCF-7 cells. In addition, aromatase induction in MCF-7 cells could also be suppressed by PD153035 hydrochloride. These results suggest that E(2) up-regulates aromatase expression by a nongenomic action of ER alpha via cross-talk with growth factor-mediated pathways.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kinoshita Y,Chen Ssubject
Has Abstractpub_date
2003-07-01 00:00:00pages
3546-55issue
13eissn
0008-5472issn
1538-7445journal_volume
63pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Microsomal epoxide hydrolase (mEH) is involved in the metabolism of tobacco-derived carcinogens. Polymorphisms in exons 3 and 4 of the EPHX gene have been reported to be associated with variations in mEH activity. We examined whether the predicted mEH activity modified the lung cancer risk among 150 cases and 172 cont...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:We examined several parameters of urine excretion during a two-year initiation-promotion experiment in male Fischer rats using four weeks of N-[4-(5-nitro-2-furyl)-2-thiazoly]formamide at 0.2% of the diet as the initiating agent and either 5% sodium saccharin or 2% L-tryptophan in the diet as promoting agents. Rats fe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-01-01 00:00:00
abstract：:The failure and/or toxicity of conventional therapies for many types of human cancers underscore the need for development of safe and effective alternative treatments. Toward this goal, we describe the direct oncolytic activity of RNA-based vectors derived from poliovirus, termed replicons, which are genetically incap...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-12-01 00:00:00
abstract：:We have demonstrated previously that the immunomodulator AS101 can protect mice from acute lethal toxicity mediated by high doses of radiation or chemotherapy. The compound was shown to rescue mice from toxic effects of cyclophosphamide or 5-fluorouracil. The results presented herein demonstrate that pretreatment of m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-12-15 00:00:00
abstract：:In November 1974, in response to a mandate in the revised National Cancer Act of 1974, a plan was introduced for the formation of a Diet, Nutrition, and Cancer Program. Dr. Frank J. Rauscher, Director of the National Cancer Institute, selected a group of scientists who defined the goals of the program and recommended ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1975-11-01 00:00:00
abstract：:The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G₂ to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SR-indep...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-1882
更新日期：2011-11-01 00:00:00
abstract：:Membrane type-1 matrix metalloproteinase (MT1-MMP) is a promising drug target in malignancy. The structure of MT1-MMP includes the hemopexin domain (PEX) that is distinct from and additional to the catalytic domain. Current MMP inhibitors target the conserved active site in the catalytic domain and, as a result, repre...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-4149
更新日期：2012-05-01 00:00:00
abstract：:Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins; however, off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally fea...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-1709
更新日期：2009-12-01 00:00:00
abstract：:Angiogenesis is essential for tumor growth and metastasis. It is regulated by numerous angiogenic factors, one of the most important being vascular endothelial growth factor (VEGF). Recently VEGF-B and VEGF-C, two new VEGF family members, have been identified that bind to the tyrosine kinase receptors flt-1 (VEGFR1), ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:Four murine monoclonal antibodies against human lung carcinoma were generated using a novel immunization procedure. BALB/c mice were rendered neonatally tolerant to normal human lung tissues and subsequently immunized with human lung tumor tissues. The lower level of antibody-reactivity to the tolerogen was seen in th...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:We have investigated the antiproliferative and cytotoxic effects of selected enediynes against three Kaposi's sarcoma (KS) cell lines. The enediynes tested were found to be very potent in inhibiting the growth of KS cells. Treatment with concentrations of 10(-10) M or less were capable of producing 50% inhibition of g...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-15 00:00:00
abstract：:Tumor-specific rosette-forming cells reactive to solubilized tumor antigens conjugated to autologous erythrocytes were quantitated by flow cytofluorometry. Leukocytes from a high frequency of the patients (greater than 70%) with squamous cell carcinoma of the head and neck (SQCC) formed rosettes to the conjugated SQCC...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-07-01 00:00:00
abstract：:This study investigated the effect of recombinant human tumor necrosis factor (rhTNF) on hydroxyl radical production by established cell lines in vitro, and its implication in the killing of tumor cells by rhTNF. During incubation of TNF sensitive mouse tumorigenic fibroblast L-M cells (2 X 10(7) cells) in the presenc...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:The p53 tumor suppressor gene product is known to be active in mediating radiation-induced G1-S cell cycle arrest and apoptosis in a number of normal cell lines. These functions are compromised by inactivation of p53, which promotes tumor progression. Because the p53 gene appears to play an important role in the cellu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
abstract：:Seventeen young women with clinically confirmed mammary dysplasia and six age-matched controls were treated with alpha-tocopherol. Serum samples collected during the luteal phase of each woman at monthly intervals for the 4-month duration of the study were analyzed for serum luteinizing hormone, follicle-stimulating h...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:When newly hatched chicks are given injections of Rous sarcoma virus, a tumor develops at the site of injection. In spite of the presence of the virus in the blood, no other tumors are found distant from the site of inoculation during the life span of the animal (4-6 weeks). However, if a wound is made away from the p...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-08-15 00:00:00
abstract：:The primary role of the mismatch repair (MMR) system is the avoidance of mutations caused by replication and recombination errors. Furthermore, the lethality of methylating agents has been attributed to the processing of O(6)-methylguanine lesions in DNA by MMR. Loss of the MSH2 protein completely abolishes repair fun...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-05-01 00:00:00
abstract：:Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat ute...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-11-01 00:00:00
abstract：:Fludarabine (9-beta-arabinofuranosyl-2-fluoroadenine-5'-monophosphate) is clinically active against chronic lymphocytic leukemia and low-grade lymphomas. We reported previously that fludarabine nucleoside synergistically enhanced cisplatin (CDDP)-induced cytotoxicity in vitro, and that the synergism was concomitant wi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-04-15 00:00:00
abstract：:Vascular endothelial growth factor D has recently been linked to the control of lymphangiogenesis and lymphatic metastasis. The molecular determinants regulating vegf-D gene transcription, however, have not yet been identified. After isolation of 2 kb of 5'-flanking DNA of the human vegf-D gene, we identified a novel,...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-5136
更新日期：2008-01-15 00:00:00
abstract：:The formation of 7-(2-hydroxyethyl)guanine (7-HEG) in DNA of target and nontarget tissues was investigated in male B6C3F1 mice (20/group) and F344 rats (10/group) exposed to 0, 3, 10, 33, 100, or 300 (rats only) ppm ethylene oxide (ETO) by inhalation for 6 h/day for 4 weeks (5 days/week) and mice exposed to 100 ppm ET...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-08-15 00:00:00
abstract：:Functional studies using freshly isolated tumor-infiltrating B lymphocytes(TIB) are difficult to perform and interpret. Here we document a novel function of TIB using fresh human lung cancer tissues engrafted in SCID mice; they are at activated state and produce tumor-specific antibodies in tumor microenvironment: (a)...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-03-15 00:00:00
abstract：:We examined whether herpes simplex virus thymidine kinase (HSV-TK) gene expression driven by the promoter of the vascular endothelial growth factor (VEGF) gene that is activated by hypoxia is effective in killing highly metastatic Lewis lung carcinoma A11 cells under hypoxic conditions. We isolated the promoter region...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-06-01 00:00:00
abstract：:The ability of the in vitro sister chromatid exchange (SCE) assay to predict in vivo tumor drug sensitivity was investigated using a spontaneous hepatocarcinoma in C3Hf/Kam mice and 3 chemotherapeutic agents: melphalan; cis-platinum; and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). For hepatocarcinoma cells grown in m...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-05-01 00:00:00
abstract：:DR-nm23 cDNA was cloned recently by differential screening of a cDNA library derived from chronic myelogenous leukemia-blast crisis primary cells. It is highly homologous to the putative metastasis suppressor nm23-H1 gene and the closely related nm23-H2 gene. When overexpressed in the myeloid precursor 32Dcl3 cell lin...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-03-15 00:00:00
abstract：:We tried to purify carcinoembryonic antigen (CEA)-related antigens in normal human feces and found that, besides nonspecific cross-reacting antigen (fecal NCA), there are three other molecular species of CEA-related antigens which have been inclusively called normal fecal antigen (NFA). These were designated normal fe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:Thirteen patients with metastatic breast carcinoma were given injections of 50-1593 micrograms of 131I-monoclonal antibody (MAb) B6.2 immunoglobulin G and F(ab')2 for pharmacokinetic evaluation and radioimmunoimaging. Blood clearance of the 131I-MAb-B6.2 was biphasic. The mean half-times (t 1/2 alpha, t 1/2 beta) for ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1986-06-01 00:00:00
abstract：:Mutations in the p53 gene were identified in five of eight non-melanoma skin tumors in the sun-exposed areas of xeroderma pigmentosum patients by the polymerase chain reaction and single strand conformation polymorphism analysis followed by sequencing of the DNA. All mutations occurred at the dipyrimidine sites, indic...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:Salmonella enterica and avirulent derivatives prefer solid tumors over normal tissue in animal models. The identification of endogenous Salmonella promoters that are preferentially activated in tumors could further our understanding of this phenomenon. Toward this goal, a random library of S. enterica typhimurium 1402...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-0552
更新日期：2008-06-15 00:00:00
abstract：:A rapid method for the measurement of serum and/or plasma, lipid-associated sialic acid levels has been developed. This test has been applied to 850 human sera of which 670 came from patients with nine categories of malignant disease, 80 from persons with benign disorders, and 100 from normal individuals. Lipid-associ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-12-01 00:00:00
