Fidelity of Runx2 activity in breast cancer cells is required for the generation of metastases-associated osteolytic disease.

Abstract:

:The osteolytic bone destruction associated with breast cancer skeletal metastases represents a serious and incurable clinical condition. However, the molecular mechanisms regulating tumor cell expression of factors involved in the generation of osteolytic disease remain elusive. We demonstrated recently that breast cancer cells express the Runx2 transcription factor, essential for bone formation and a regulator of skeletal homeostasis. Our experimental results demonstrate that perturbation of Runx2 regulatory function in tumor cells abolishes their ability to form osteolytic lesions in vivo. In vitro, we show that breast cancer cells inhibit osteoblast differentiation while concurrently enhancing osteoclast differentiation in marrow stromal cell cultures. Disruption of Runx2 activity abrogates both of these cancer cell-mediated effects on bone cells. These results demonstrate that Runx2 expression in breast cancer cells provides a molecular phenotype that enables the interactions between tumor cells and the bone microenvironment that lead to osteolytic disease.

journal_name

Cancer Res

journal_title

Cancer research

authors

Barnes GL,Hebert KE,Kamal M,Javed A,Einhorn TA,Lian JB,Stein GS,Gerstenfeld LC

doi

10.1158/0008-5472.CAN-03-3851

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

4506-13

issue

13

eissn

0008-5472

issn

1538-7445

pii

64/13/4506

journal_volume

64

pub_type

杂志文章
  • Sequencing of trimodality therapy [cis-diamminedichloroplatinum(II)/hyperthermia/radiation] as determined by tumor growth delay and tumor cell survival in the FSaIIC fibrosarcoma.

    abstract::In order to improve local control of tumors over that achievable with local hyperthermia and radiation, we are testing the use of systemic cis-diamminedichloroplatinum(II) (CDDP) in conjunction with the other two modalities. In the FSaIIC fibrosarcoma, growth delay experiments indicated that the use of any two modalit...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Herman TS,Teicher BA

    更新日期:1988-05-15 00:00:00

  • Effect of stathmin on the sensitivity to antimicrotubule drugs in human breast cancer.

    abstract::Stathmin is a p53-regulated protein known to influence microtubule dynamics. Because several chemotherapeutic agents used to treat breast cancer alter the dynamic equilibrium of tubulin polymerization, stathmin may play an important role in determining the sensitivity to these drugs. Therefore, we evaluated the effect...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Alli E,Bash-Babula J,Yang JM,Hait WN

    更新日期:2002-12-01 00:00:00

  • Transcriptional programs following genetic alterations in p53, INK4A, and H-Ras genes along defined stages of malignant transformation.

    abstract::The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impedes our understanding of the malignant transformation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studie...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-3880

    authors: Milyavsky M,Tabach Y,Shats I,Erez N,Cohen Y,Tang X,Kalis M,Kogan I,Buganim Y,Goldfinger N,Ginsberg D,Harris CC,Domany E,Rotter V

    更新日期:2005-06-01 00:00:00

  • Cancer suppression at old age.

    abstract::Increased age is regularly linked with heightened cancer risk, but recent research suggests a flattening around age 80. We report that, independent of cancer site or time period, most incidence rates decrease in the more elderly and drop to or toward zero near the ceiling of human life span. For all major organ sites,...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1670

    authors: Harding C,Pompei F,Lee EE,Wilson R

    更新日期:2008-06-01 00:00:00

  • Near haploid cell line in lymphoid blast crisis of Ph1-positive chronic myeloid leukemia.

    abstract::This report describes a case of lymphoid blast crisis of a chronic myelocytic leukemia with the occurrence of a double chromosomal population carrying a Philadelphia chromosome. Fifty-five % of the cells have 28 chromosomes, and 36% show the exact duplicate of the near haploid chromosome complement. The similarities b...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kessous A,Colombies P,Pris J,Clement D

    更新日期:1980-04-01 00:00:00

  • Antivasculature effects of doxorubicin-containing liposomes in an intracranial rat brain tumor model.

    abstract::Increased neovascularization and vascular hyperpermeability are integral processes in tumors, and various therapeutic strategies seek to reverse the angiogenic phenotype. Long-circulating liposomes extravasate in tumors such as the rat 9L gliosarcoma and accumulate in perivascular areas. Under such conditions, liposom...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhou R,Mazurchuk R,Straubinger RM

    更新日期:2002-05-01 00:00:00

  • Spontaneous regressive epitheliomas in the Japanese newt, Cynops pyrrhogaster.

    abstract::Spontaneous tumors in urodele amphibians have been considered uncommon, and this resistance has sometimes been associated with the natural regenerative capacity of tissues in such species. This report describes spontaneous, nonpigmented, benign epitheliomas which were found in 44 of 1586 (2.8%) adult newts, Cynops pyr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Pfeiffer CJ,Nagai T,Fujimura M,Tobe T

    更新日期:1979-06-01 00:00:00

  • Treatment of glioma by engineered interleukin 4-secreting cells.

    abstract::The ability of interleukin-4 (IL-4) to mediate an antitumor response to human gliomas was studied in vivo in nude mice. To allow the effect of IL-4 to be exerted over a relatively short distance and at an optimal concentration, a transfected tumor cell line expressing a high level of IL-4 was used in mixed tumor trans...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yu JS,Wei MX,Chiocca EA,Martuza RL,Tepper RI

    更新日期:1993-07-01 00:00:00

  • Signal transducer and activator of transcription 1 activation in endothelial cells is a negative regulator of angiogenesis.

    abstract::To determine the role of the transcription factor signal transducer and activator of transcription (STAT) 1 on endothelial cell function, human umbilical vein endothelial cells (HUVEC) were treated with IFN-gamma, a potent activator of STAT1. IFN-gamma inhibited cell growth and tube formation of HUVECs. Although the p...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3612

    authors: Battle TE,Lynch RA,Frank DA

    更新日期:2006-04-01 00:00:00

  • Nuclear Receptor LRH-1 Functions to Promote Castration-Resistant Growth of Prostate Cancer via Its Promotion of Intratumoral Androgen Biosynthesis.

    abstract::Targeting of steroidogenic enzymes (e.g., abiraterone acetate targeting CYP17A1) has been developed as a novel therapeutic strategy against metastatic castration-resistant prostate cancer (CRPC). However, resistance to steroidal inhibitors inevitably develops in patients, the mechanisms of which remain largely unknown...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-2341

    authors: Xiao L,Wang Y,Xu K,Hu H,Xu Z,Wu D,Wang Z,You W,Ng CF,Yu S,Chan FL

    更新日期:2018-05-01 00:00:00

  • Incidence and nature of tumors induced in Sprague-Dawley rats by gamma-irradiation.

    abstract::In our previous studies carried out on inbred rats of the Sprague-Dawley strain (L. Gross and Y. Dreyfuss, Proc. Natl. Acad. Sci. USA, 76: 5910-5913, 1979), the tumor incidence was increased following irradiation (150 rads, 5 times, at weekly intervals), from 22 to 93% in females and from 5 to 59% in males. Experiment...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gross L,Dreyfuss Y,Faraggiana T

    更新日期:1988-05-01 00:00:00

  • Transformation nonresponsive cells owe their resistance to lack of p65/nuclear factor-kappaB activation.

    abstract::Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. I...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hsu TC,Nair R,Tulsian P,Camalier CE,Hegamyer GA,Young MR,Colburn NH

    更新日期:2001-05-15 00:00:00

  • MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions.

    abstract::MicroRNAs are noncoding RNAs that inhibit the expression of their targets in a sequence-specific manner and play crucial roles during oncogenesis. Here we show that microRNA-7 (miR-7) inhibits p21-activated kinase 1 (Pak1) expression, a widely up-regulated signaling kinase in multiple human cancers, by targeting the 3...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-2103

    authors: Reddy SD,Ohshiro K,Rayala SK,Kumar R

    更新日期:2008-10-15 00:00:00

  • Definition of molecular determinants of prostate cancer cell bone extravasation.

    abstract::Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells ex...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-12-3264

    authors: Barthel SR,Hays DL,Yazawa EM,Opperman M,Walley KC,Nimrichter L,Burdick MM,Gillard BM,Moser MT,Pantel K,Foster BA,Pienta KJ,Dimitroff CJ

    更新日期:2013-01-15 00:00:00

  • Fragmented sleep accelerates tumor growth and progression through recruitment of tumor-associated macrophages and TLR4 signaling.

    abstract::Sleep fragmentation (SF) is a highly prevalent condition and a hallmark of sleep apnea, a condition that has been associated with increased cancer incidence and mortality. In this study, we examined the hypothesis that sleep fragmentation promotes tumor growth and progression through proinflammatory TLR4 signaling. In...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-13-3014

    authors: Hakim F,Wang Y,Zhang SX,Zheng J,Yolcu ES,Carreras A,Khalyfa A,Shirwan H,Almendros I,Gozal D

    更新日期:2014-03-01 00:00:00

  • Nuclear factor-kappaB and manganese superoxide dismutase mediate adaptive radioresistance in low-dose irradiated mouse skin epithelial cells.

    abstract::Mechanisms governing inducible resistance to ionizing radiation in untransformed epithelial cells pre-exposed to low-dose ionizing radiation (LDIR;

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-2728

    authors: Fan M,Ahmed KM,Coleman MC,Spitz DR,Li JJ

    更新日期:2007-04-01 00:00:00

  • Overexpression of metalloproteinase inhibitor in B16F10 cells does not affect extravasation but reduces tumor growth.

    abstract::It is widely accepted that a major role of matrix metalloproteinases in the metastatic process is degradation of basement membrane during cancer cell invasion. We tested the hypothesis that the reduction in metastatic potential which has been demonstrated for B16F10 melanoma cells genetically engineered to overexpress...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Koop S,Khokha R,Schmidt EE,MacDonald IC,Morris VL,Chambers AF,Groom AC

    更新日期:1994-09-01 00:00:00

  • Nitric oxide mediates Kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: a comparison with oxidative burst.

    abstract::The metabolic changes in rat hepatoma cell line, AH70 cells, after coculturing with Kupffer cells were visualized using a silicon-intensified target camera and subsequent processing with a computer-assisted digital imaging processor. In cocultured tumor cells, nonactivated Kupffer cells reduced mitochondrial energizat...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kurose I,Miura S,Fukumura D,Yonei Y,Saito H,Tada S,Suematsu M,Tsuchiya M

    更新日期:1993-06-01 00:00:00

  • Protein kinase Cepsilon is linked to 12-O-tetradecanoylphorbol-13-acetate-induced tumor necrosis factor-alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase Cepsilon transgenic mice.

    abstract::Protein kinase Cepsilon (PKCepsilon), a Ca(2+)-independent, phospholipid-dependent serine/threonine kinase, is among the PKC isoforms expressed in mouse epidermis. We reported that FVB/N transgenic mice that overexpress ( approximately 18-fold) PKCepsilon protein in basal epidermal cells and cells of the hair follicle...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Wheeler DL,Ness KJ,Oberley TD,Verma AK

    更新日期:2003-10-01 00:00:00

  • Anti-CD20 Therapy Acts via FcγRIIIA to Diminish Responsiveness of Human Natural Killer Cells.

    abstract::Natural killer (NK) immune cells mediate antibody-dependent cellular cytotoxicity (ADCC) by aggregating FcγRIIIA/CD16, contributing significantly to the therapeutic effect of CD20 monoclonal antibodies (mAb). In this study, we show that CD16 ligation on primary human NK cells by the anti-CD20 mAb rituximab or ofatumum...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-15-0781

    authors: Capuano C,Romanelli M,Pighi C,Cimino G,Rago A,Molfetta R,Paolini R,Santoni A,Galandrini R

    更新日期:2015-10-01 00:00:00

  • Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors.

    abstract::Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Matsukura S,Kakita T,Sueoka S,Yoshimi H,Hirata Y,Yokota M,Fujita T

    更新日期:1980-10-01 00:00:00

  • Reactive Oxygen Species Drive Proliferation in Acute Myeloid Leukemia via the Glycolytic Regulator PFKFB3.

    abstract::Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a poor clinical outcome. Previously, we showed that overproduction of reactive oxygen species (ROS), arising from constitutive activation of NOX2 oxidase, occurs in >60% of patients with AML and that ROS production promotes proliferation of AML cells...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-19-1920

    authors: Robinson AJ,Hopkins GL,Rastogi N,Hodges M,Doyle M,Davies S,Hole PS,Omidvar N,Darley RL,Tonks A

    更新日期:2020-03-01 00:00:00

  • Influence of pH on the thermal sensitivity of cultured human glioblastoma cells.

    abstract::The hyperthermic sensitivity of cultured human glioblastoma cells was determined in 1 degree increments from 42 through 46 degrees over the pH range of 6.1 to 7.4. These cells were 5 to 10 times less heat sensitive than were Chinese hamster ovary cells and are among the most resistant cells examined in cell culture. A...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Gerweck LE,Richards B

    更新日期:1981-03-01 00:00:00

  • Potentiation of etoposide-induced DNA damage by calcium antagonists in L1210 cells in vitro.

    abstract::Verapamil and a number of other Ca2+ antagonists were found to potentiate DNA damage induced by 4'-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-beta-D-glucop yra noside (VP-16) in L1210 cells in vitro. The potentiating effect of verapamil on DNA single-strand breaks in vitro was concentration dependent, relevant to ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yalowich JC,Ross WE

    更新日期:1984-08-01 00:00:00

  • Metabolism of benzo(a)pyrene by human epithelial cells in vitro.

    abstract::Primary cell cultures derived from human skin epithelium metabolized benzo(a)pyrene to three classes of compounds: phenols, quinones, and dihydrodiols. The relative proportions of metabolites varied according to the skin donor but differed from the pattern of metabolites in rat liver microsome preparations. While appr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Fox CH,Selkirk JK,Price FM,Croy RG,Sanford KK,Cottler-Fox M

    更新日期:1975-12-01 00:00:00

  • The activated Notch1 signal pathway is associated with gastric cancer progression through cyclooxygenase-2.

    abstract::Gastric carcinoma is one of the most common cancers and lethal malignancies worldwide. Thus far, the regulatory mechanisms of its aggressiveness are still poorly understood. To understand the pathogenesis and to develop new therapeutic strategies, it is essential to dissect the molecular mechanisms that regulate progr...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-08-4021

    authors: Yeh TS,Wu CW,Hsu KW,Liao WJ,Yang MC,Li AF,Wang AM,Kuo ML,Chi CW

    更新日期:2009-06-15 00:00:00

  • Prostaglandin H synthase-catalyzed metabolism and DNA binding of 2-naphthylamine.

    abstract::The oxidation of the bladder carcinogen 2-naphthylamine (2-NA) by prostaglandin H synthase (PHS) in vitro was examined. Oxygen uptake studies of 2-NA oxidation in the presence of glutathione, as well as extensive product analysis data, are consistent with a one-electron mechanism of 2-NA oxidation by PHS. The formatio...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Boyd JA,Eling TE

    更新日期:1987-08-01 00:00:00

  • Altered expression of c-IAP1, survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells.

    abstract::Resistance to chemotherapy predicts an unfavorable outcome for patients with radioiodine-insensitive thyroid cancer. To investigate the mechanisms underlying this resistance, we evaluated the expression of four different inhibitor of apoptosis proteins, and their antagonist, Smac, in thyroid cancer cells that survived...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-05-3248

    authors: Tirrò E,Consoli ML,Massimino M,Manzella L,Frasca F,Sciacca L,Vicari L,Stassi G,Messina L,Messina A,Vigneri P

    更新日期:2006-04-15 00:00:00

  • Induction of muscle protein degradation and weight loss by a tumor product.

    abstract::Splenocytes from mice bearing a cachexia-inducing tumor (MAC16) have been fused with mouse myeloma cells to produce hybridomas, which have been cloned to produce antibody reactive to a material which copurified with a lipid-mobilizing factor isolated from the same tumor. The monoclonal antibody has been used to invest...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Todorov PT,McDevitt TM,Cariuk P,Coles B,Deacon M,Tisdale MJ

    更新日期:1996-03-15 00:00:00

  • The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma.

    abstract::Somatic copy number variations (CNV) may drive cancer progression through both coding and noncoding transcripts. However, noncoding transcripts resulting from CNV are largely unknown, especially for circular RNAs. By integrating bioinformatics analyses of alerted circRNAs and focal CNV in lung adenocarcinoma, we ident...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-17-2808

    authors: Qiu M,Xia W,Chen R,Wang S,Xu Y,Ma Z,Xu W,Zhang E,Wang J,Fang T,Hu J,Dong G,Yin R,Wang J,Xu L

    更新日期:2018-06-01 00:00:00