Abstract:
:Several studies have shown that E-cadherin expression is lost during malignant transformation. We hypothesized that CpG methylation in the promoter region may inactivate the expression of the E-cadherin gene in human bladder cancer. Normal and bladder cancer samples from 51 patients were compared in terms of E-cadherin gene expression and methylation status by immunohistochemistry, methylation-specific polymerase chain reaction (MSP), and bisulfite genome-sequencing techniques. Ten different CpG sites (nt 863, 865, 873, 879, 887, 892, 901, 918, 920, and 940) in the promoter region were studied. Thirty-five of 51 (69%) bladder cancer samples lacked E-cadherin expression, whereas only six of 51 (12%) normal bladder samples lacked E-cadherin immunoreactivity. MSP analysis of bladder cancer samples suggested that 43 of 51 (84%) showed methylation of the promoter region, whereas only 12 of 51 (24%) normal bladder samples showed hypermethylation. Sodium bisulfite genome-sequencing analysis revealed that of 10 CpG sites, two sites (nt 892 and nt 940) showed 100% methylation in all the cancer samples analyzed. Other CpG sites were partially methylated (47-91%). Normal tissue showed only 12% methylation (range, 1-33%) on various CpG sites. Also supporting these data, E-cadherin-negative bladder cancer cell lines restored expression of the E-cadherin gene after treatment with the demethylating agent 5-aza-2'-deoxycytidine. The present study showed that CpG hypermethylation was an important mechanism of E-cadherin gene inactivation in bladder cancer and also that specific CpG sites consistently presented higher methylation levels than others. These findings may provide a better strategy for the diagnosis and management of bladder cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Ribeiro-Filho LA,Franks J,Sasaki M,Shiina H,Li LC,Nojima D,Arap S,Carroll P,Enokida H,Nakagawa M,Yonezawa S,Dahiya Rdoi
10.1002/mc.10064subject
Has Abstractpub_date
2002-08-01 00:00:00pages
187-98issue
4eissn
0899-1987issn
1098-2744journal_volume
34pub_type
杂志文章abstract::KITLG/KIT pathway plays a vital role in multiple types of human cancer including head and neck squamous cell carcinoma (HNSCC). Genetic variations in KITLG and KIT may affect the expression or function of these genes, thereby modifying cancer risk. In this study, we evaluated the association of KITLG and KIT polymorph...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22487
更新日期:2017-01-01 00:00:00
abstract::Metformin, an oral biguanide for the treatment of type II diabetes, has been shown to have anticancer effects in ovarian cancer. Energy starvation induced by metformin causes endoplasmic reticulum stress-mediated unfolded protein response (UPR) and autophagy. UPR and autophagy act as a survival or death mechanism in c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22284
更新日期:2016-04-01 00:00:00
abstract::In the present study, we evaluated the effect of deleting Twist1 on keratinocyte proliferation and on skin tumor development using the two-stage chemical carcinogenesis model. BK5.Cre × Twist1(flox/flox) mice, which have a keratinocyte-specific Twist1 knockout (Twist1 KO), developed significantly reduced numbers of pa...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22335
更新日期:2016-05-01 00:00:00
abstract::This study examines the relationship between p53 immunostaining and direct sequencing of polymerase chain reaction (PCR) products in 61 gliomas. Glioma tissues obtained from patients at surgery were analyzed immunohistochemically with the monoclonal antibody PAb1801 to detect p53 protein abnormalities. Amplified p53 c...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199601)15:1<1::AID-MC1>3.0
更新日期:1996-01-01 00:00:00
abstract::Polymorphisms of the base excision repair gene APE1 may be associated with an increased risk for developing prostate cancer. In other cancer types, altered APE1 protein expression is a candidate prognostic marker. Using immunohistochemistry, we thus analyzed APE1 expression in 9763 prostate cancers in a tissue microar...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22670
更新日期:2017-09-01 00:00:00
abstract::Obesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20720
更新日期:2011-05-01 00:00:00
abstract::The mutational specificity of the cyclic nitrosamine N-nitrosopyrrolidine (NPYR) was determined through the DNA sequence characterization of 33 lacl-d mutations of Escherichia coli. Base substitution was the predominant class of mutation induced (91%). The majority of these (64%) occurred at GC base pairs, in accordan...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940030304
更新日期:1990-01-01 00:00:00
abstract::Bcl-x(L) is one of several antiapoptotic proteins regulated by signal transducer and activator of transcription 3 (Stat3). We have recently shown that Stat3 is required for chemically induced and ultraviolet B (UVB)-induced skin carcinogenesis. In this study, the functional role of Bcl-x(L) in skin carcinogenesis was ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20527
更新日期:2009-10-01 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::The physical gut barrier, comprised of a thick mucus layer and the epithelium, plays an important role in defense against microbes and foreign antigens. Calcium and vitamin D may be involved in maintaining the integrity of the intestinal mucosal barrier, the dysfunction of which may lead to endotoxemia and inflammatio...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1002/mc.23010
更新日期:2019-07-01 00:00:00
abstract::C>T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C>T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas st...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22623
更新日期:2017-06-01 00:00:00
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 atten...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.1067
更新日期:2001-10-01 00:00:00
abstract::Ultraviolet (UV) light-induced activation of activator protein-1 (AP-1), resulting at least in part from oxidative stress, promotes skin carcinogenesis. It has not yet been determined whether elevating cellular phase II enzymes and glutathione (GSH) levels inhibits the AP-1 activation. We have, therefore, examined the...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20052
更新日期:2004-11-01 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::Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogen...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22700
更新日期:2017-12-01 00:00:00
abstract::Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21976
更新日期:2014-02-01 00:00:00
abstract::DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5' regulatory regions in the promoter, exon 1, and intron 1 were differe...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20100
更新日期:2005-07-01 00:00:00
abstract::We evaluated whether high-fat diet (HFD), in the absence of increased calorie intake, increases colon cancer growth and metastasis. Four-week-old male BALB/c mice were fed on an HFD (60 kcal% fat) or control diet (10 kcal% fat) for 16 wk, after which CT26 colon cancer cells were subcutaneously injected into the right ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20856
更新日期:2012-11-01 00:00:00
abstract::In our previous study, we showed that miR-125a directly targeted a WT1 oncogene, which was overexpressed in leukemia and various kinds of solid tumors including lung, breast, gastric, and colon cancers, and brain tumors and was deeply involved in leukemogenesis and tumorigenesis and that miR-125a knockout mice overexp...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22446
更新日期:2016-12-01 00:00:00
abstract::The Ron receptor tyrosine kinase is overexpressed in approximately half of all human colon cancers. Increased Ron expression positively correlates with tumor progression, and reduction of Ron levels in human colon adenocarcinoma cells reverses their tumorigenic properties. Nearly all colon tumors demonstrate loss of t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20551
更新日期:2009-11-01 00:00:00
abstract::In this report, we describe in detail the evolving procedures to optimize humanized mouse cohort generation, including optimal conditioning, choice of lineage for engraftment, threshold for successful engraftment, HNSCC tumor implantation, and immune and stroma cell analyses. We developed a dual infusion protocol of h...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22887
更新日期:2018-11-01 00:00:00
abstract::High-level expression of the c-sis oncogene, which encodes the beta chain of platelet-derived growth factor, transforms immortalized rodent fibroblasts in vitro to a malignant phenotype. c-sis gene expression has been demonstrated in a variety of human tumors, although generally at levels much lower than those shown t...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050412
更新日期:1992-01-01 00:00:00
abstract::Polymorphisms in metabolic and DNA repair genes may alter protein function, consequently affecting patients' response to chemo/radiotherapy. We retrospectively assessed whether polymorphisms of glutathione-S-transferase genes GSTM1 (deletion), GSTT1 (deletion), GSTP1 (Ile105Val, rs1695), and DNA repair genes hOGG1 (Se...
journal_title:Molecular carcinogenesis
pub_type: 临床试验,杂志文章
doi:10.1002/mc.21868
更新日期:2012-10-01 00:00:00
abstract::The aim of this study was to test whether long-term ethanol consumption confers therapeutic resistance to human liver cancer patients infected with hepatitis B virus (HBV). Chronic ethanol-treated cells were established by consecutively culturing a human hepatocellular carcinoma cell line, Hep 3B, which contains integ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20648
更新日期:2010-08-01 00:00:00
abstract::The extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK) pathway is an important cell proliferation pathway. We previously reported that the transport protein particle complex 4 (TRAPPC4), ERK2 interaction may activate ERK1/2, modulate pERK2 nuclear localization and regulate proliferati...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22031
更新日期:2014-02-01 00:00:00
abstract::Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20664
更新日期:2010-10-01 00:00:00
abstract::Cr(VI) causes severe kidney damage. The patient's renal function could gradually recover by spontaneous kidney regeneration. The molecular effect of Cr(VI) on recovery of kidney cells, however, has not been clearly elucidated. Here we show that Cr(VI) induces expression of mesenchymal and stem cell markers, cell marke...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22268
更新日期:2016-02-01 00:00:00
abstract::Krüppel-like factor 4 (KLF4) is a zinc-finger-containing transcription factor with tumor suppressor activity in various cancer types. Cells that sustain double strand breaks (DSBs) in their DNA due to high levels of reactive oxygen species (ROS) can develop genomic instability, which can result in cancer formation. On...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22161
更新日期:2015-09-01 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::Signaling networks play important roles in cancer progression. For example, overexpression of the epidermal growth factor receptor (EGFR) is a poor prognostic indicator in multiple tumor types. Recent studies have postulated that the EGFR functions as a central conduit for signaling by different classes of cell surfac...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20138
更新日期:2005-12-01 00:00:00