Abstract:
:We confirmed the expression of cathepsin K, the most abundant and specific cysteine protease found in osteoclasts, at the mRNA level in most of our cases of breast cancer, and even at the protein level in bone metastatic lesions. Therefore, we investigated the functions of cathepsin K in osteoclasts with special attention to bone metastasis from breast cancer. Mouse osteoclast-like cells (OCLs) were established by coculture of mouse bone marrow cells and osteoblastic cells. Rodent cathepsin K antisense (AS) or random control (CL) oligonucleotides were added on day 0, 3, or 6 of culture. Tartrate-resistant acid phosphatase staining confirmed the formation of OCLs after 9 d of incubation. AS treatment significantly reduced both the number of TRAP-positive cells and the percentage of multinuclear cells. For the pit-forming assay, after 9 d of incubation, mature OCLs were collected and incubated on ivory slices with AS or CL for 48 h. The antisense oligonucleotides also inhibited the bone-resorbing activity of OCLs. CL treatment did not affect either the number of TRAP-positive cells or pit formation. Cathepsin K may play important roles in bone resorption as well as in differentiation of osteoclasts. These findings indicate that the inhibition of this enzyme may prevent the development of bone metastasis from breast cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Ishikawa T,Kamiyama M,Tani-Ishii N,Suzuki H,Ichikawa Y,Hamaguchi Y,Momiyama N,Shimada Hdoi
10.1002/mc.1067subject
Has Abstractpub_date
2001-10-01 00:00:00pages
84-91issue
2eissn
0899-1987issn
1098-2744pii
10.1002/mc.1067journal_volume
32pub_type
杂志文章abstract::Flavonoids are the most investigated phytochemicals due to their pharmacological and therapeutic activities. Their ability to chelate with metal ions has resulted in the emergence of a new category of molecules with a broader spectrum of pharmacological activities. In this study, the ruthenium quercetin complex has be...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22792
更新日期:2018-06-01 00:00:00
abstract::RAD51D, a paralog of the mammalian RAD51 gene, contributes towards maintaining genomic integrity by homologous recombination DNA repair and telomere maintenance. A RAD51D variant, E233G, was initially identified as a potential susceptibility allele in high-risk, site-specific, familial breast cancer. We describe in th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20545
更新日期:2009-07-01 00:00:00
abstract::We previously reported that two dietary regimens, calorie restriction (CR) and a high olive oil-containing diet supplemented with a freeze-dried fruit and vegetable extract (OFV), reduced the development of intestinal adenomas in Apc(Min) mice by 57% and 33%, respectively, compared to control mice fed a defined diet a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20233
更新日期:2007-01-01 00:00:00
abstract::Although carcinoma of the uterine endometrium is the most frequently diagnosed malignancy of the female reproductive tract, the molecular genetic features of this tumor have yet to be described in significant detail. Since mutations of the p53 tumor suppressor gene are the single most common genetic alteration found i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050403
更新日期:1992-01-01 00:00:00
abstract::Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long-term positive effects are very poor. Aurora B ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22993
更新日期:2019-06-01 00:00:00
abstract::Canonical Wnt signaling is altered in most cases of colorectal cancer. Experimental evidence indicates that protein phosphatase 2A (PP2A) may play either positive or negative roles in Wnt signaling but its precise in vivo functions remain elusive. In this work, using colon cultured cell lines we showed that basal PP2A...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22217
更新日期:2015-11-01 00:00:00
abstract::Angiogenesis plays an important role in growth, progression, and metastasis of tumors. The most important regulator of angiogenesis is vascular endothelial growth factor (VEGF). VEGF expression has been associated with advance stage and poor survival of several cancers. In the present study we evaluated the associatio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20495
更新日期:2009-06-01 00:00:00
abstract::The abnormal expression of adipocyte enhancer binding protein 1 (AEBP1) has been implicated in the carcinogenesis and progression of various types of human tumors. However, the role of AEBP1 in colon adenocarcinoma (COAD) remains largely unelucidated. In this study, we explored the clinical significance and biological...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23066
更新日期:2019-10-01 00:00:00
abstract::To explore the mechanisms through which hypoxic tumor microenvironment (TME) modulates the transition of tumor-associated macrophages (TAMs). The migration ability of RAW264.7 macrophages was determined by transwell assay. Flow cytometric, western blot and immunofluorescence analyses of CD206 further validated the M2 ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22936
更新日期:2019-03-01 00:00:00
abstract::Polyamine metabolism is a highly coordinated process that is essential for normal development and neoplastic growth in mammals. Although polyamine metabolism is a validated pathway for prevention of carcinogenesis, the mechanisms by which polyamines elicit their tumorigenic effects are poorly understood. In this study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22051
更新日期:2014-02-01 00:00:00
abstract::Tocopherols, the major forms of vitamin E, are a family of fat-soluble compounds that exist in alpha (α-T), beta (β-T), gamma (γ-T), and delta (δ-T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α-T, the most a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22481
更新日期:2017-01-01 00:00:00
abstract::Dietary prevention is a cost-efficient strategy to reduce the risk of human cancers. More than 85% breast cancers are sporadic and attributable to long-term exposure to environmental carcinogens through a multistep and multiyear disease process. We used our chronically induced cellular carcinogenesis model as a target...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21970
更新日期:2014-03-01 00:00:00
abstract::Barrett's metaplasia consists of columnar epithelium that replaces the normal esophageal mucosa in patients with chronic gastroesophageal reflux. Because intestinal-type Barrett's metaplasia is the major risk factor for adenocarcinoma development, understanding the mechanisms that predispose the esophageal mucosa to m...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199902)24:2<128::aid-mc7>3
更新日期:1999-02-01 00:00:00
abstract::Breast cancer-associated mutations affecting the highly-conserved C-terminal BRCT domains of the tumor suppressor gene breast cancer susceptibility gene 1 (BRCA1) fully disrupt the ability of BRCA1 to interact with acetyl coenzyme A carboxylase alpha (ACCA), the rate-limiting enzyme catalyzing de novo fatty acid bioge...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20364
更新日期:2008-02-01 00:00:00
abstract::Although it is known that cells transformed by ras and other oncogenes show reduced gap junction function, to date there has been no investigation of the quantitative relationship between intracellular levels of ras oncoprotein and loss of cell-cell communication. Using the rat liver epithelial cell line MTR6, which c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050307
更新日期:1992-01-01 00:00:00
abstract::The number of validated biomarkers of tobacco smoke exposure is limited, and none exist for tobacco-related cancer. Additional biomarkers for smoke, effects on cellular systems in vivo are needed to improve early detection of lung cancer, and to assist the Food and Drug Administration in regulating exposures to tobacc...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22385
更新日期:2016-10-01 00:00:00
abstract::Serially transplantable rat mammary tumor (RMT) cells are not dependent on exogenous epidermal growth factor (EGF) and insulin-like growth factor-I for continuous growth in serum-free medium. Previously, we found that conditioned medium obtained from these cells contained EGF-like mitogenic activity and stimulated tyr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199602)15:2<134::AID-MC6>3
更新日期:1996-02-01 00:00:00
abstract::The influence of the tumor promoter 2-acetylaminofluorene (2-AAF) on cell proliferation and on the epidermal growth factor receptor (EGFR) system was assessed in normal and nodular rat livers. DNA replication in vivo was inhibited below the detection level after 8d of dietary 2-AAF treatment of previously unexposed ra...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100207
更新日期:1994-06-01 00:00:00
abstract::2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) are carcinogens found in cooked meats that form DNA adducts upon metabolic activation. Purified DNA from Chinese hamster ovary (CHO) cells was reacted in vitro with the active metabolites N-acetoxy-IQ or N-acetoxy-Me...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940070211
更新日期:1993-01-01 00:00:00
abstract::The majority of ovarian cancers over-express the estrogen receptor (ERα) and grow in response to estrogens. We previously demonstrated that ER induction of the chemokine CXCL12 (stromal cell-derived factor-1) is required for estradiol (E2)-stimulated proliferation of human ovarian carcinoma cells. In the current study...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21913
更新日期:2013-09-01 00:00:00
abstract::Extrachromosomal replication of viral DNA sequences has been observed in transformed as well as in normal cells following "stress"-inducing treatments. To explore the effect of growth conditions on the ability to support such replication, we analyzed SEWA sarcoma cells that grew subcutaneously or as ascites tumors in ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030506
更新日期:1990-01-01 00:00:00
abstract::The Ki-ras proto-oncogene is activated by specific point mutations and is the transforming gene often identified in rodent and human lung tumors. An in vitro model to aid in the study of the consequences of Ki-ras activation and expression in mouse lung is needed. Accordingly, we have examined cell lines derived from ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030508
更新日期:1990-01-01 00:00:00
abstract::Epidermal growth factor receptor (EGFR) plays an important role in the development and progression of lung cancer. A previous report noted that an increased number of polymorphic CA repeats in the first intron of the EGFR gene results in decreased transcriptional activity. To estimate the association of the length of ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20285
更新日期:2007-05-01 00:00:00
abstract::Estrogen is thought to be an important etiologic agent in endometrial and breast cancers. However, the mechanism or mechanisms by which estrogen acts as a hormonal carcinogen are not well understood. We hypothesize that in response to chronic exposure to estrogens, human endometrial stromal fibroblasts (ESF) produce f...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199812)23:4<217::aid-mc4>3
更新日期:1998-12-01 00:00:00
abstract::Non-alcoholic steatohepatitis (NASH) is becoming one of the major causes of hepatocellular carcinoma (HCC) in the United States and Western countries; however, the molecular mechanisms associated with NASH-related liver carcinogenesis are not well understood. In the present study, we investigated cancer-associated chr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22818
更新日期:2018-08-01 00:00:00
abstract::The expression of members of the family of matrix-degrading metalloproteinases (MMPs) is believed to contribute to the complex process of invasion and metastasis. In this study, specific cDNA probes for three members of the stromelysin subfamily of MMPs--stromelysin (MMP-3), stromelysin-2 (MMP-10), and pump-1 (MMP-7)-...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940040617
更新日期:1991-01-01 00:00:00
abstract::Resistance to cisplatin-based chemotherapy is responsible for the majority of deaths from head and neck squamous cell carcinoma (HNSCC). In this study, using genome-wide gene expression analysis to investigate potential molecular mediators of HNSCC chemoresistance, we identified SERPINB2, a known inhibitor of extracel...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22033
更新日期:2014-10-01 00:00:00
abstract::Differentiation antagonizing non-protein coding RNA (DANCR) is a newly identified oncogenic long noncoding RNA found in various cancers. However, the functional role of DANCR in tumor angiogenesis and the underlying mechanisms are still unclear. The expression of DANCR was determined in ovarian malignant tissues and c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23117
更新日期:2019-12-01 00:00:00
abstract::Our previous study demonstrated that phosphatidylinositol 3-kinase (PI3K) is necessary for epidermal growth factor (EGF)-induced cell transformation in mouse epidermal JB6 cells. Akt and the mammalian target of rapamycin (mTOR) are regarded as PI3K downstream effectors. Therefore, in this study, we investigated the ro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10140
更新日期:2003-09-01 00:00:00
abstract::Parafibromin, encoded by the gene HRPT2, is a tumor suppressor protein associated with the RNA polymerase II-associated complex, Paf1 complex. HRPT2 mutations were first identified in patients with the multiple endocrine neoplasia syndrome, hyperparathyroidism-jaw tumor (HPT-JT) syndrome, and have also been found in s...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20591
更新日期:2010-03-01 00:00:00