Abstract:
:The proto-oncogene, c-src, has been implicated in the tumorigenesis in breast cancer. However, the relationship of c-src with distant metastasis is unclear. Moreover, the role of c-src in organ-preferential metastasis of breast cancer is unknown. Because breast cancer has a strong predilection for metastasizing to bone, we examined the role of c-src in bone metastases using an animal model in which inoculation of the MDA-231 human breast cancer cells into the left cardiac ventricle preferentially developed osteolytic bone metastases in female nude mice. A clone of the MDA-231 with the increased capacity of bone metastasis exhibited elevated c-src tyrosine kinase (TK) activity compared with parental cells. MDAsrc527 cells caused significantly increased size of the osteolytic bone metastases with increased number of osteoclasts and mitotic cancer cells compared with MDA-231EV or MDAsrcWT. In contrast, MDAsrc295 cells caused impaired metastases to bone. Of note, mice inoculated with MDAsrc295 cells via tail vein developed reduced lung metastases and prolonged survival compared with mice with MDA-231EV cells, suggesting that c-src TK is unlikely to play a specific role in bone metastases. The growth in vitro and in vivo and production of parathyroid hormone-related protein, a key cytokine in the pathogenesis of osteolytic bone metastases in breast cancer, were promoted in MDAsrc527 and diminished in MDAsrc295. These results suggest that c-src TK is associated with the capacity of breast cancer to metastasize to bone through regulating cell growth and parathyroid hormone-related protein production. Our results together with the fact that c-src is an essential molecule for bone resorption by osteoclasts, which are central players in osteolytic bone metastases, support the notion that c-src TK is a potential target molecule for designing novel therapeutic interventions, especially for bone metastases in breast cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Myoui A,Nishimura R,Williams PJ,Hiraga T,Tamura D,Michigami T,Mundy GR,Yoneda Tsubject
Has Abstractpub_date
2003-08-15 00:00:00pages
5028-33issue
16eissn
0008-5472issn
1538-7445journal_volume
63pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Activated ras oncogene transfection into suitable recipient cells has been shown to induce the metastatic phenotype (Thorgeirsson, et al., Mol. Cell. Biol., 5: 259-262, 1985). We have used this model system to study the correlation of basement membrane collagenolysis with metastatic propensity. The c-Ha-ras oncogene a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-03-15 00:00:00
abstract::Isolated mitochondria from highly glycolytic Ehrlich and AS30-D tumor cells have a 12.4- and a 2.3-fold higher cholesterol level, respectively, than that of rat liver mitochondria. The passive proton permeability of Ehrlich and AS30-D tumor inner membrane mitochondria is, respectively, 4- and 1.4-fold lower than that ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-15 00:00:00
abstract::EWS encodes a ubiquitously expressed RNA binding protein with largely unknown function. In Ewing sarcoma family tumors (EFT), one allele is rearranged with an ETS gene. This is the first description of an EFT with a complete EWS deficiency in the presence of two copies of a rearranged chromosome 22 carrying an interst...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-15 00:00:00
abstract::Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor is expressed at higher levels in a variety of human carcinomas than it is in adjacent normal tissue. The higher expression is associated with an increase of intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. W...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-10-01 00:00:00
abstract::High expression of VEGFC predicts adverse prognosis in acute myeloid leukemia (AML). We therefore explored VEGFC-targeting efficacy as an AML therapy using a VEGFC mAb. VEGFC antibody therapy enforced myelocytic differentiation of clonal CD34+ AML blasts. Treatment of CD34+ AML blasts with the antibody reduced expansi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0250
更新日期:2018-10-15 00:00:00
abstract::That ferritin, an iron storage protein, can be produced by neuroblastoma cells raises the possibility that iron may have some role in promoting tumor cell growth. To explore this possibility, we studied the effects of desferoxamine, a compound which chelates iron, on viability of CHP 126 and CHP 100, two human neurobl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-04-01 00:00:00
abstract::Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Me...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1269
更新日期:2008-07-15 00:00:00
abstract::Shionogi carcinoma 115 (SC115) has been accepted for 20 years as an androgen-responsive mouse mammary tumor. However, we and others recently found that the growth of SC115 cells is also stimulated by high doses of glucocorticoids. We already reported the following findings. In a serum-free medium [Ham's F-12: Eagle's ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-09-15 00:00:00
abstract::Interleukin-6 (IL-6) is a pleiotropic cytokine with a broad range of physiologic and pathologic functions. Because in cancer, IL-6 contributes to a microenvironment that promotes tumor cell survival, angiogenesis, and inflammation, understanding the mechanism responsible for its production is important. In neuroblasto...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-2165
更新日期:2012-05-01 00:00:00
abstract::Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricte...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-17-1788
更新日期:2018-02-15 00:00:00
abstract::This report describes an early and direct action of oncogenic agents and its apparent consequences. Chemical carcinogen has been found to interact principally with a specific polypeptide in livers of normal rats. Short-term ingestion of carcinogen causes marked reductions in the concentrations of both the carcinogen:p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::c-myc expression, amplification, and rearrangement were studied in neoplastic hepatic nodules of rats after diethylnitrosamine treatment, in hepatocellular carcinomas induced by N-methyl-N-nitrosourea, and in tumorigenic liver cell lines derived from rat hepatocytes transformed by diethylnitrosamine in vivo. Steady-st...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-12-01 00:00:00
abstract::The modifying effects of antioxidants were examined in a carcinogenesis system after N,N-dibutylnitrosamine treatment. Male F344 rats were given 0.05% N,N-dibutylnitrosamine in their drinking water for 4 wk and then treated with basal diet containing 2% butylated hydroxyanisole (BHA), 1% butylated hydroxytoluene (BHT)...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-04-15 00:00:00
abstract::The breakpoint of t(11;14)(q23;q32) chromosome translocation in a B-cell lymphoma line, RC-K8, was cloned. Immunoglobulin heavy chain (IGH) constant gene, C gamma 2 at the 5' end, was involved in this translocation, and the DNA segment juxtaposed to the C gamma 2 was proved to be derived from chromosome 11 by somatic ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::Recent characterization of abnormal phosphatidylcholine metabolism in tumor cells by nuclear magnetic resonance (NMR) has identified novel fingerprints of tumor progression that are potentially useful as clinical diagnostic indicators. In the present study, we analyzed the concentrations of phosphatidylcholine metabol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1146
更新日期:2005-10-15 00:00:00
abstract::In vivo studies have shown that inhibitors of cyclooxygenase metabolism of arachidonic acid may diminish growth and metastasis of certain tumors. Because cyclooxygenase inhibition may increase the production of lipoxygenase products of arachidonic acid metabolism, we have investigated the effect of two such products, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The effect of the AC33 tumor on protein synthesis in Lewis-Wistar rats was investigated under four different dietary regimens. The four diets used were: (a) 1.25 g amino acids plus 12.5 g glucose per day, (b) 1.25 g amino acids, (c) 1.25 g glucose per day, and (d) 12.5 g glucose per day. The rats were maintained on th...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Mucin 1 (MUC1), a bound mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic carcinoma. Evidence suggests that MUC1 can be used as a tumor marker and is a potential target for immunotherapy of pancreatic cancer. However, vaccination with MUC1 peptides fails to stimulate t...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-4313
更新日期:2010-07-01 00:00:00
abstract::The concept that different leukemias are developmentally distinct and, like in normal hematopoiesis, generated by restricted populations of cells named leukemia-initiating cells (LIC), is becoming more established. These cancer stem-like cells have been assumed to have unique properties, including the capability of se...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-20-2571
更新日期:2021-01-07 00:00:00
abstract::Activation of the matrix metalloproteinase 2 (MMP-2) has been shown to play a major role in the proteolysis of extracellular matrix (ECM) associated with tumor invasion. Although the precise mechanism of this activation remains elusive, levels of the membrane type 1-MMP (MT1-MMP) at the cell surface and of the tissue ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-12-01 00:00:00
abstract::Malignant glioma is an often fatal type of cancer. Aberrant activation of STAT3 leads to glioma tumorigenesis. STAT3-induced transcription of protein-coding genes has been extensively studied; however, little is known about STAT3-regulated miRNA gene transcription in glioma tumorigenesis. In this study, we found that ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3073
更新日期:2016-07-15 00:00:00
abstract::LMO2 is a transcription regulator involved in human T-cell leukemia, including some occurring in X-SCID gene therapy trials, and in B-cell lymphomas and prostate cancer. LMO2 functions in transcription complexes via protein-protein interactions involving two LIM domains and causes a preleukemic T-cell development bloc...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-4774
更新日期:2009-06-01 00:00:00
abstract::Epidemiological studies have shown a positive association of colon cancer with hyperlipidemia. Furthermore, signaling generated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma ligands, suggested to be candidate tumor preventive agents, has been shown to lower serum triglyceride levels. In the pres...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-09-15 00:00:00
abstract::The presence of tumor cells in the circulation may predict disease recurrence and metastases. We have developed a sensitive technique for the detection of carcinoma cells in blood, using immunomagnetic beads to enrich for epithelial cells and the polymerase chain reaction to identify a tumor marker. The colon carcinom...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::Low-grade serous ovarian carcinoma (LGSOC) is a rare tumor subtype with high case fatality rates in patients with metastatic disease. There is a pressing need to develop effective treatments using newly available preclinical models for therapeutic discovery and drug evaluation. Here we use multiomics integration of wh...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-2222
更新日期:2021-01-13 00:00:00
abstract::Acquired resistance to cisplatin has been generated in vitro in two human ovarian carcinoma cell lines: 41M, established from a previously untreated patient; and CH1, from a patient previously treated with cisplatin and cis-diammine-1,1-cyclobutane dicarboxylatoplatinum(II) (carboplatin). In neither cell line with acq...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-07-15 00:00:00
abstract::Of six prostatic carcinoma cell lines examined (ALVA31, DU145, JCA1, LNCaP, ND1, and PC3) by flow cytometric analysis, all were found to be positive for Fas antigen. Furthermore, of the prostate tissue specimens studied (six cases), all revealed Fas expression in benign and malignant epithelial cells. The agonistic an...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::Although mutated forms of ras are not associated with the majority of breast cancers (<5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine w...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0396
更新日期:2004-07-01 00:00:00
abstract::Triple-negative breast cancer (TNBC) is an aggressive clinical subtype accounting for up to 20% of all breast cancers, but its malignant determinants remain largely undefined. Here, we show that in TNBC the overexpression of Fra-1, a component of the transcription factor AP-1, offers prognostic potential. Fra-1 deplet...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-3396
更新日期:2014-07-15 00:00:00
abstract::Experiments were performed to determine if differences in porphyrin photosensitivity could be observed for cells with varying efficiency in DNA damage repair, as well as for cells which make up components of the vasculature. Photofrin II is undergoing current clinical evaluation for photodynamic therapy of solid tumor...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-15 00:00:00