Abstract:
:Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15R beta) in cytokine-independent cell lines established from radiation-induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL-2/15R beta alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP-IL2/15R beta chimeric gene expressed chimeric mRNA in which IAP-coding Gag-Pol mRNA was fused to IL-2/15R beta mRNA and coded for Gag-Pol-IL-2/15R beta chimeric protein. Forced expression of the Gag-Pol-IL-2/15R beta chimeric cDNA in a mouse cytotoxic T-cell line (CTLL-2) converted IL-2-dependent cell growth to IL-2-independent growth, suggesting that the chimeric protein activates some of the IL-2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag-Pol-IL-2/15R beta chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c-myc protein. These results suggest that the Gag-Pol-IL-2/15R beta is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c-myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL-2-independent autonomous growth potential.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Ukai H,Ishii-Oba H,Ukai-Tadenuma M,Ogiu T,Tsuji Hdoi
10.1002/mc.10128subject
Has Abstractpub_date
2003-06-01 00:00:00pages
110-9issue
2eissn
0899-1987issn
1098-2744journal_volume
37pub_type
杂志文章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::Alterations in the transforming growth factor-beta (TGF-beta) pathway are implicated in the pathogenesis of colorectal cancer. We hypothesize that alterations in the TGF-beta pathway contribute to differential sensitivity of mice to the colon carcinogen azoxymethane (AOM). A/J (sensitive) and AKR/J (resistant) mice we...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.1055
更新日期:2001-08-01 00:00:00
abstract::Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to show this happens in esophageal neoplasms. To examine the expression of this integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal epithelium, ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::The DNA repair gene Ku70 plays a key role in the DNA double strand break (DSB) repair system. Defects in DSB repair capacity can lead to genomic instability. We hypothesized that the Ku70 C-1310G polymorphism (rs2267437) was associated with risk of renal cell carcinoma (RCC). We genotyped the Ku70 C-1310G polymorphism...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21914
更新日期:2012-10-01 00:00:00
abstract::Genomic DNA sequences with the ability to assume non-B form secondary structures have been recently shown to be particularly susceptible to genetic instability, an early contributing factor in human disease and cancer development. Transcription appears to play a central role in formation of these structures and in pro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.20513
更新日期:2009-04-01 00:00:00
abstract::Identification of long noncoding RNA (lncRNA) expression quantitative trait loci (lncR-eQTL) that associated with lung cancer can provide insights into regulatory mechanisms of lncRNA, and help reveal the role of lncRNA in lung cancer. A two-stage case-control design was implemented in this study. We first selected th...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23013
更新日期:2019-07-01 00:00:00
abstract::We investigated the in vitro effects of pyrogallol on cell growth, cell cycle regulation, and apoptosis in HeLa cells. Pyrogallol inhibited the growth of HeLa cells with an IC(50) of approximately 45 microM. Pyrogallol induced arrest during all phases of the cell cycle and also very efficiently resulted in apoptosis i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20369
更新日期:2008-02-01 00:00:00
abstract::Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.23255
更新日期:2020-11-01 00:00:00
abstract::The majority of human neoplasms have aberrations in the retinoblastoma pathway due to hyperactivation of cyclin-dependent kinases (CDK). Based on this observation, novel small molecules, such as flavopiridol and UCN-01, are being developed and are currently being tested in the clinic. Efforts to develop CDK modulators...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10114
更新日期:2003-04-01 00:00:00
abstract::In this paper, patterns of allelic imbalances (Als) in chemically induced rat mammary, colon, and bladder tumors from (Wistar Furth x Fischer 344)F1 rats are described and compared. Male F1 rats were administered azoxymethane (AOM), and colon tumors were collected at 58 wk after treatment. Female F1 rats were given ei...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199901)24:1<47::aid-mc7>3.
更新日期:1999-01-01 00:00:00
abstract::Benzo[alpha]pyrene-7,8-diol-9,10-epoxide (B[a]PDE), the major metabolite of benzo[a]pyrene (B[a]P), shows an ultimate complete carcinogen in various animals and is a causative agent for human cancers. However, its effects on the activation of signal pathways and the expression of genes involved in its carcinogenic eff...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20260
更新日期:2007-01-01 00:00:00
abstract::Loss of heterozygosity (LOH) on the long arm of chromosome 13 is common in human breast tumors, pointing to the existence of several suppressor genes in this region. LOH at 13q14 has been implicated in alterations of retinoblastoma gene (RB1) expression. However, attempts to identify a link between the absence of reti...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Using relatively primitive tools in the 1920s, Otto Warburg demonstrated that tumor cells show an increased dependence on glycolysis to meet their energy needs, regardless of whether they were well-oxygenated or not. High rates of glucose uptake, fueling glycolysis, are now used clinically to identify cancer cells. Ho...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.21863
更新日期:2013-05-01 00:00:00
abstract::The P53 gene is a tumor suppressor gene and can prevent mutation and tumor induction though apoptosis and DNA repair when it is activated by genotoxic stress. miR-34a expression is regulated by the P53 gene and might be required for cell response to DNA damage. TK6 cells are human lymphoblast cells with normal P53 fun...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20830
更新日期:2012-08-01 00:00:00
abstract::The normal function of excision repair cross complementing group 1 (ERCC1) is essential for maintaining genomic integrity and preventing cellular neoplastic transformation, and multiple studies have reported an association between ERCC1 polymorphisms and increased risk of cancers. To test whether the genetic variants ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,随机对照试验
doi:10.1002/mc.20468
更新日期:2009-03-01 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::Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expres...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22928
更新日期:2019-02-01 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::Epithelial-mesenchymal transition (EMT) is an embryonic program that is reactivated in cancer and regulates the invasion and metastasis of tumor cells. Zinc finger E-box binding homeobox 2 (ZEB2) induces EMT by upregulating matrix metalloproteinases (MMP), yet MMP genes lack ZEB2 binding motif in their promoters. Rece...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22994
更新日期:2019-06-01 00:00:00
abstract::Patulin (PAT), a present day major contaminant of commercial apple and apple products is reported to be carcinogenic, embryotoxic, and immunotoxic. While oral and inhalation are considered to be the most prevalent routes of exposure to this toxin, exposure through skin is now being extensively investigated. Our previo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22060
更新日期:2014-12-01 00:00:00
abstract::Liver cirrhosis is a critical state in the natural course of hepatocellular carcinoma (HCC). We sought to investigate the potential of in-depth proteomics to reveal plasma protein signatures that reflect common networks/pathways of liver cirrhosis, and to determine whether the cirrhosis-related signature in plasma is ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21952
更新日期:2014-01-01 00:00:00
abstract::The tyrosinase promoter has been used to target expression of the mutated human T24 Ha-ras oncogene in pigment-producing cells of transgenic mice. Two independent founder mice carrying the transgene survived and showed the same distinct phenotype of mutated coat color, deeply pigmented skin with multiple nevi, and twi...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940120205
更新日期:1995-02-01 00:00:00
abstract::Development of chemoresistance in androgen-refractory prostate cancer cells is partly due to constitutive activation of Rel/NF-kappaB transcription factors that regulate several cell survival and anti-apoptotic genes. In this study we examined whether betulinic acid (BetA), a pentacyclic triterpene from the bark of wh...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20447
更新日期:2008-12-01 00:00:00
abstract::Altered c-Ha-ras genes have been frequently detected in the DNA of spontaneous or chemically induced mouse liver tumors. To determine if ras gene mutation is a frequent event during liver carcinogenesis in rats, we examined the transforming activity of DNA from liver tumors that developed in rats injected with methyl(...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010108
更新日期:1988-01-01 00:00:00
abstract::The interplay between cancer cells and the normal surrounding tissue is believed to influence the biological behavior of the tumor. However, the presence of multiple cell types within the prelevated tumor specimen may attenuate changes that occur specifically in the malignant cells within their microenvironment. To st...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20055
更新日期:2004-12-01 00:00:00
abstract::Angiogenesis is a prerequisite for progression of cancers. The number of genes linked to angiogenesis suggests the existence of complex gene-networks, which remain to be elucidated. To identify angiogenesis genes deregulated in carcinomas, we performed a meta-profiling analysis of published gene expression microarray ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,meta分析
doi:10.1002/mc.20874
更新日期:2013-01-01 00:00:00
abstract::Some of the progeny of isolated mouse embryo fibroblasts acquire the ability to grow indefinitely during cultivation, presumably through some mutational events. The relevance of p53 mutations and loss of heterozygosity to the mechanism of such immortal growth capability remains controversial. Since four bases in intro...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940100109
更新日期:1994-05-01 00:00:00
abstract::Heat shock protein 60 (HSP60) overexpresses in various types of cancer, but its expression levels and functions in hepatocellular carcinoma (HCC) are still in dispute. We aim to clarify this issue and examine whether HSP60 could be a therapeutic target for HCC. We found drastically enhanced cell apoptosis and suppress...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22827
更新日期:2018-09-01 00:00:00
abstract::Tamoxifen (TAM) is widely used in the treatment and prevention of breast cancer. There is clear evidence that cytochrome P450 (CYP) 3A enzymes play an important role in TAM metabolism, resulting in metabolites that lead to formation of TAM-DNA adducts. We have investigated the effect of CYP3A2 antisense (AVI-4472) exp...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20143
更新日期:2006-02-01 00:00:00
abstract::Formation of G4 DNA may occur in the course of replication and transcription, and contribute to genomic instability. We have quantitated abundance of G4 motifs and potential for G4 DNA formation of the nontemplate strand of 5' exons and introns of transcripts of human genes. We find that, for all human genes, G4 motif...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20496
更新日期:2009-04-01 00:00:00