EphA2 overexpression decreases estrogen dependence and tamoxifen sensitivity.

Abstract:

:The EphA2 receptor tyrosine kinase is found at low levels on nontransformed adult breast epithelial cells but is frequently overexpressed on aggressive breast cancer cells. Recent studies have documented an inverse relationship between EphA2 and estrogen receptor expression in breast cancer cell lines. In our present study, we demonstrate that overexpression of EphA2 decreases estrogen dependence as defined using both in vitro and in vivo criteria. The EphA2-transfected cells demonstrate increased growth in vitro and form larger and more aggressive tumors in vivo. EphA2 overexpression also decreases the ability of tamoxifen to inhibit breast cancer cell growth and tumorigenesis. These effects of EphA2 overexpression can be overcome by antibody-based targeting of EphA2. In particular, certain EphA2 antibodies can resensitize EphA2-overexpressing breast tumor cells to tamoxifen. These results have important implications for understanding the molecular basis underlying estrogen dependence and provide further evidence that EphA2 may provide a much-needed therapeutic target for breast cancer.

journal_name

Cancer Res

journal_title

Cancer research

authors

Lu M,Miller KD,Gokmen-Polar Y,Jeng MH,Kinch MS

subject

Has Abstract

pub_date

2003-06-15 00:00:00

pages

3425-9

issue

12

eissn

0008-5472

issn

1538-7445

journal_volume

63

pub_type

杂志文章
  • Biological behavior of malignant melanoma cells correlated to their survival in vivo.

    abstract::Successive B16 melanoma tumor lines were selected for their ability to form pulmonary tumor nodules. This was accomplished by injecting tumor cells i.v. into syngeneic C57BL/6 mice and 2 to 3 weeks later collecting the secondary tumor growths and placing them into tissue culture. These tumor cells were then injected i...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fidler IJ

    更新日期:1975-01-01 00:00:00

  • Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas.

    abstract::We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ li...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Garcia I,Dietrich PY,Aapro M,Vauthier G,Vadas L,Engel E

    更新日期:1989-12-01 00:00:00

  • Comparative Analysis of Bispecific Antibody and Streptavidin-Targeted Radioimmunotherapy for B-cell Cancers.

    abstract::Streptavidin (SA)-biotin pretargeted radioimmunotherapy (PRIT) that targets CD20 in non-Hodgkin lymphoma (NHL) exhibits remarkable efficacy in model systems, but SA immunogenicity and interference by endogenous biotin may complicate clinical translation of this approach. In this study, we engineered a bispecific fusio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-0571

    authors: Green DJ,Frayo SL,Lin Y,Hamlin DK,Fisher DR,Frost SH,Kenoyer AL,Hylarides MD,Gopal AK,Gooley TA,Orozco JJ,Till BG,O'Steen S,Orcutt KD,Wilbur DS,Wittrup KD,Press OW

    更新日期:2016-11-15 00:00:00

  • Identification of a p53-dependent negative response element in the bcl-2 gene.

    abstract::Recently, we have shown that the p53 tumor suppressor gene product can inhibit expression of the bcl-2 gene. In this report, we explored the molecular basis for p53-mediated down-regulation of bcl-2 gene expression using a cotransfection approach involving p53 expression plasmids and chloramphenicol acetyltransferase ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Miyashita T,Harigai M,Hanada M,Reed JC

    更新日期:1994-06-15 00:00:00

  • Castration-induced apoptosis of androgen-dependent shionogi carcinoma is associated with increased expression of genes encoding insulin-like growth factor-binding proteins.

    abstract::Insulin-like growth factor (IGF)-I has well-characterized mitogenic and antiapoptotic effects that are essential for maintenance of the normal prostate and may be important during regression of the normal prostate and/or prostate tumors induced by androgen-targeting therapies for prostate cancer. IGF-I activity is mod...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Nickerson T,Miyake H,Gleave ME,Pollak M

    更新日期:1999-07-15 00:00:00

  • Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies.

    abstract::Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-1617

    authors: Lee HS,Lee NC,Kouprina N,Kim JH,Kagansky A,Bates S,Trepel JB,Pommier Y,Sackett D,Larionov V

    更新日期:2016-02-15 00:00:00

  • Activation of Rap1 promotes prostate cancer metastasis.

    abstract::Elucidating the mechanisms of prostate cancer (CaP) survival and metastasis are critical to the discovery of novel therapeutic targets. The monomeric G protein Rap1 has been implicated in cancer tumorigenesis. Rap1 signals to pathways involved in cell adhesion, migration, and survival, suggesting Rap1 may promote seve...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-4269

    authors: Bailey CL,Kelly P,Casey PJ

    更新日期:2009-06-15 00:00:00

  • Effects of the antitumor agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3 H)-one on the DNA of mouse L1210 cells.

    abstract::L1210 murine leukemia cells were treated in vitro with the novel antineoplastic agent 8-carbamoyl-3-(2-chloroethyl)imidazo[5,1-d] -1,2,3,5-tetrazin-4(3H)-one (M&B 39565), and its interaction with cellular DNA was assessed by alkaline elution. DNA interstrand cross-link and DNA-protein cross-link formation was quantifi...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gibson NW,Erickson LC,Hickman JA

    更新日期:1984-05-01 00:00:00

  • The reversal of methotrexate cytotoxicity to mouse bone marrow cells by leucovorin and nucleosides.

    abstract::The cytotoxic effect of methotrexate (MTX) for mouse bone marrow cells has been studied by in vitro of the granulocyte precursor cell (CFU-C) in a medium containing dialyzed fetal calf serum and dialyzed L-cell supernatant. The formation of 50-cell colonies was inhibited to 50% of control by 10(-8) M MTX. Further incr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Pinedo HM,Zaharko DS,Bull JM,Chabner BA

    更新日期:1976-12-01 00:00:00

  • Evolutionary Action Score of TP53 Coding Variants Is Predictive of Platinum Response in Head and Neck Cancer Patients.

    abstract::TP53 is the most frequently altered gene in head and neck squamous cell carcinoma (HNSCC), with mutations occurring in over two thirds of cases; however, the predictive response of these mutations to cisplatin-based therapy remains elusive. In the current study, we evaluate the ability of the Evolutionary Action score...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-14-2729

    authors: Osman AA,Neskey DM,Katsonis P,Patel AA,Ward AM,Hsu TK,Hicks SC,McDonald TO,Ow TJ,Alves MO,Pickering CR,Skinner HD,Zhao M,Sturgis EM,Kies MS,El-Naggar A,Perrone F,Licitra L,Bossi P,Kimmel M,Frederick MJ,Lichtarge

    更新日期:2015-04-01 00:00:00

  • Sensitization of mesothelioma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by heat stress via the inhibition of the 3-phosphoinositide-dependent kinase 1/Akt pathway.

    abstract::Heat stress may enhance the effect of apoptosis-inducing agents in resistant tumor cells. One such agent is the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which has attracted intense interest for its ability to induce apoptosis in tumors without affecting nonmalignant cells. We therefore tested w...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-3871

    authors: Pespeni MH,Hodnett M,Abayasiriwardana KS,Roux J,Howard M,Broaddus VC,Pittet JF

    更新日期:2007-03-15 00:00:00

  • Analysis of DNA adducts in putative premalignant hepatic nodules and nontarget tissues of rats during 2-acetylaminofluorene carcinogenesis.

    abstract::Exposure of rats to a standard four-cycle feeding regimen of 0.06% 2-acetylaminofluorene (AAF) results in the formation of putatively premalignant hepatic nodules, but the types and magnitude of DNA adducts formed in these nodules has not been previously examined. By using a sensitive 32P-adduct assay (R. C. Gupta, Ca...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gupta RC,Earley K,Becker FF

    更新日期:1988-09-15 00:00:00

  • DNA sequence specificity of doxorubicin-induced mutational damage in uvrB- Escherichia coli.

    abstract::In the absence of excision repair, doxorubicin caused a striking (41-fold) increase in the frequency of large deletion mutations extending from the lac operator (lacO) into the lac repressor gene (lacI) of Escherichia coli. In contrast, there was only a 2-fold increase in the frequency of small deletions despite a 3-f...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Anderson RD,Veigl ML,Baxter J,Sedwick WD

    更新日期:1991-08-01 00:00:00

  • Immune function of patients with gastrointestinal carcinoma after treatment with multiple infusions of monoclonal antibody 17.1A.

    abstract::Ten patients with metastatic adenocarcinomas of the colon or pancreas were treated with multiple injections of monoclonal antibody 17.1A. For each injection, antibody concentration in the patients' sera plateaued during the entire treatment course, and then decreased, with faster antibody clearance in patients given p...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Blottière HM,Maurel C,Douillard JY

    更新日期:1987-10-01 00:00:00

  • Expression pattern of chemokine receptor 6 (CCR6) and CCR7 in squamous cell carcinoma of the head and neck identifies a novel metastatic phenotype.

    abstract::Squamous cell carcinoma of the head and neck (SCCHN) metastasizes predictably to cervical lymph nodes, with low rates of distant metastases. Tumor cells can express various receptors that facilitate such metastatic spread to lymph nodes and other nonlymphoid organs. Chemokine receptors (CCR), normally expressed on lym...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.can-03-2968

    authors: Wang J,Xi L,Hunt JL,Gooding W,Whiteside TL,Chen Z,Godfrey TE,Ferris RL

    更新日期:2004-03-01 00:00:00

  • Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness.

    abstract::Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in pri...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-09-2654

    authors: Chigurupati S,Venkataraman R,Barrera D,Naganathan A,Madan M,Paul L,Pattisapu JV,Kyriazis GA,Sugaya K,Bushnev S,Lathia JD,Rich JN,Chan SL

    更新日期:2010-01-01 00:00:00

  • A syngeneic variance library for functional annotation of human variation: application to BRCA2.

    abstract::The enormous scope of natural human genetic variation is now becoming defined. To accurately annotate these variants, and to identify those with clinical importance, is often difficult to assess through functional assays. We explored systematic annotation by using homologous recombination to modify a native gene in he...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-6189

    authors: Hucl T,Rago C,Gallmeier E,Brody JR,Gorospe M,Kern SE

    更新日期:2008-07-01 00:00:00

  • Array comparative genomic hybridization analysis of genomic alterations in breast cancer subtypes.

    abstract::In this study, we performed high-resolution array comparative genomic hybridization with an array of 4153 bacterial artificial chromosome clones to assess copy number changes in 44 archival breast cancers. The tumors were flow sorted to exclude non-tumor DNA and increase our ability to detect gene copy number changes....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-1992

    authors: Loo LW,Grove DI,Williams EM,Neal CL,Cousens LA,Schubert EL,Holcomb IN,Massa HF,Glogovac J,Li CI,Malone KE,Daling JR,Delrow JJ,Trask BJ,Hsu L,Porter PL

    更新日期:2004-12-01 00:00:00

  • Overexpression and overactivation of Akt in thyroid carcinoma.

    abstract::Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequen...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ringel MD,Hayre N,Saito J,Saunier B,Schuppert F,Burch H,Bernet V,Burman KD,Kohn LD,Saji M

    更新日期:2001-08-15 00:00:00

  • p73beta-Mediated apoptosis requires p57kip2 induction and IEX-1 inhibition.

    abstract::Similarly to p53, p73alpha and p73beta induce growth arrest and/or apoptosis in response to DNA damage or when exogenously expressed. However, how they trigger apoptosis remains unresolved. After stable transduction of either p73alpha or p73beta, a greater apoptotic response was observed for p73beta in both primary an...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3047

    authors: Gonzalez S,Perez-Perez MM,Hernando E,Serrano M,Cordon-Cardo C

    更新日期:2005-03-15 00:00:00

  • Identification and intracellular location of MAGE-3 gene product.

    abstract::The human MAGE-3 gene encodes a melanoma antigenic epitope recognized by specific cytotoxic T lymphocytes, but its gene product has not been identified thus far. We produced a recombinant MAGE-3 gene product by expression cloning of the entire reading frame in the context of a fusion protein characterized by a 10-hist...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kocher T,Schultz-Thater E,Gudat F,Schaefer C,Casorati G,Juretic A,Willimann T,Harder F,Heberer M,Spagnoli GC

    更新日期:1995-06-01 00:00:00

  • Antiangiogenic agent sunitinib transiently increases tumor oxygenation and suppresses cycling hypoxia.

    abstract::Structural and functional abnormalities in tumor blood vessels impact the delivery of oxygen and nutrients to solid tumors, resulting in chronic and cycling hypoxia. Although chronically hypoxic regions exhibit treatment resistance, more recently it has been shown that cycling hypoxic regions acquire prosurvival pathw...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-2025

    authors: Matsumoto S,Batra S,Saito K,Yasui H,Choudhuri R,Gadisetti C,Subramanian S,Devasahayam N,Munasinghe JP,Mitchell JB,Krishna MC

    更新日期:2011-10-15 00:00:00

  • Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer.

    abstract::In ovarian cancer, the immune system fails to eradicate established tumors partly due to the induction of immune tolerance within tumor microenvironment. In this study, we investigated the contribution of plasmacytoid dendritic cells (pDC) in the establishment of immune tolerance in a cohort of 44 ovarian cancer patie...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-11-0367

    authors: Labidi-Galy SI,Sisirak V,Meeus P,Gobert M,Treilleux I,Bajard A,Combes JD,Faget J,Mithieux F,Cassignol A,Tredan O,Durand I,Ménétrier-Caux C,Caux C,Blay JY,Ray-Coquard I,Bendriss-Vermare N

    更新日期:2011-08-15 00:00:00

  • MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth.

    abstract::MicroRNAs (miRNA) are a recently discovered class of noncoding RNAs that negatively regulate gene expression. Recent evidence indicates that miRNAs may play an important role in cancer. However, the mechanism of their deregulation in neoplastic transformation has only begun to be understood. To elucidate the role of t...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1585

    authors: Corney DC,Flesken-Nikitin A,Godwin AK,Wang W,Nikitin AY

    更新日期:2007-09-15 00:00:00

  • Humanized Mouse Xenograft Models: Narrowing the Tumor-Microenvironment Gap.

    abstract::Cancer research has long been hampered by the limitations of the current model systems. Both cultured cells and mouse xenografts grow in an environment highly dissimilar to that of their originating tumor, frequently resulting in promising treatments that are ultimately clinically ineffective. The development of highl...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-16-1260

    authors: Morton JJ,Bird G,Refaeli Y,Jimeno A

    更新日期:2016-11-01 00:00:00

  • Establishment of a human megakaryoblastic cell line (T-33) from chronic myelogenous leukemia in megakaryoblastic crisis.

    abstract::A megakaryoblastic cell line, termed T-33, was established from the peripheral blood of a patient with Philadelphia chromosome-positive chronic myelogenous leukemia in megakaryoblastic crisis. T-33 cells have been maintained in RPMI 1640 medium containing 10% fetal calf serum in a single cell suspension with a doublin...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Tange T,Nakahara K,Mitani K,Yamasaki I,Yasuda H,Tanaka F,Mizuguchi M,Oda H,Yatomi Y,Takanashi R

    更新日期:1988-11-01 00:00:00

  • Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction.

    abstract::In the present study, we assessed the susceptibility of freshly isolated neuroblastoma cells to killing mediated by normal human natural killer (NK) cells and analyzed the receptor-ligand interactions that regulate this event. We show that killing of freshly isolated neuroblasts, similar to neuroblastoma cell lines, i...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-2682

    authors: Castriconi R,Dondero A,Corrias MV,Lanino E,Pende D,Moretta L,Bottino C,Moretta A

    更新日期:2004-12-15 00:00:00

  • Mutations of the bak gene in human gastric and colorectal cancers.

    abstract::The Bcl-2 homologue Bak is a potent inducer of apoptosis. We performed PCR-based single-strand conformational polymorphism and sequencing analysis of the entire coding region of the bak gene (exons 2-6) in 24 primary gastric cancers (6 early-stage and 18 advanced-stage cancers) and 20 primary colorectal cancers (6 ear...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kondo S,Shinomura Y,Miyazaki Y,Kiyohara T,Tsutsui S,Kitamura S,Nagasawa Y,Nakahara M,Kanayama S,Matsuzawa Y

    更新日期:2000-08-15 00:00:00

  • Micronuclei Frequency in Tumors Is a Predictive Biomarker for Genetic Instability and Sensitivity to the DNA Repair Inhibitor AsiDNA.

    abstract::Therapeutic strategies targeting DNA repair pathway defects have been widely explored, but often only benefit small numbers of patients. Here we characterized potential predictive biomarkers for treatment with AsiDNA, a novel first-in-class DNA repair inhibitor. We evaluated genetic instability and DNA repair defects ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-16-2693

    authors: Jdey W,Thierry S,Popova T,Stern MH,Dutreix M

    更新日期:2017-08-15 00:00:00

  • Increased glucocorticoid receptor concentration in macrophage differentiation of myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate.

    abstract::HL60 cells, human promyelocytic leukemia cells, can be induced to differentiate into more mature myeloid forms by dimethyl sulfoxide (DMSO) or retinoic acid (RA) and into macrophage-like cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) or related compounds. Macrophage differentiation of HL60 cells by TPA treatment ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hirai H,Murakami T,Urabe A,Takaku F

    更新日期:1985-06-01 00:00:00