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 effect remain largely unknown. In this study, the effects of B[a]PDE on induction of cyclooxygenase (COX)-2 and the signal pathways leading to the induction were investigated. Treatment of mouse epidermal Cl41 cells with B[a]PDE caused an increase in the expression of COX-2 at both transcription and protein levels, while its parental compound B[a]P did not show significant inductive effect. The COX-2 induction by B[a]PDE was dependent on the activation of mitogen-activated protein kinases (MAPK)s/activation protein (AP)-1 pathway, because inhibition of AP-1 by either overexpression of TAM67 (dominant negative mutant of c-jun), or pretreatment of cells with PD98059 (MEK1/2-ERKs pathway inhibitor) or SB202190 (p38K inhibitor), markedly inhibited B[a]PDE-induced COX-2 expression. In addition, impairment of NF-kappaB pathway by either NEMO-BDBP (an NF-kappaB specific inhibitor) or IkappaB kinase (IKK)beta-KM (dominant negative mutant of IKKbeta) also caused marked reduction of COX-2 induction by B[a]PDE. In contrast, inhibition of nuclear factor of activated T cells (NFAT) with FK506, did not show any effect on B[a]PDE-induced COX-2 expression. Collectively, these data indicate that exposure of Cl41 cells to B[a]PDE can induce COX-2 expression by increasing its transcription, which requires the activation of MAPKs/AP-1 and IKKbeta/NF-kappaB pathways, but not NFAT pathway. In view of the importance of COX-2 in carcinogenesis, we anticipate that the induction of COX-2 by B[a]PDE may coordinate its mutagenic effects to facilitate the development of skin cancer.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Ouyang W,Ma Q,Li J,Zhang D,Ding J,Huang Y,Xing MM,Huang Cdoi
10.1002/mc.20260subject
Has Abstractpub_date
2007-01-01 00:00:00pages
32-41issue
1eissn
0899-1987issn
1098-2744journal_volume
46pub_type
杂志文章abstract::Angelica gigas Nakai (AGN) root ethanol extract exerts anti-cancer activity in several allograft and xenograft models. Here we examined its chemopreventive efficacy through gavage administration against primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Male C57BL/6 TRAMP mice and...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22230
更新日期:2015-12-01 00:00:00
abstract::The vaccinia virus cDNA expression system was used to produce human cytochrome P450 IA2 in a hepatoma cell line that is devoid of significant basal levels of P450. The expressed enzyme yielded a reduced carbon monoxide-bound difference spectrum with a lambda max of 449 nm. Catalytic activities and mutagen activation a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940020405
更新日期:1989-01-01 00:00:00
abstract::Aberrant microRNA (miRNA) expression is involved in tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). Furthermore, expression of some miRNAs has been shown to be under epigenetic regulation. However, less is known regarding the role of miRNA methylation in NSCLC development or clinical ou...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22149
更新日期:2015-06-01 00:00:00
abstract::Studies show that elevated insulin-like growth factor-1 (IGF-1) levels are associated with an increased risk of breast cancer; however, mechanisms through which IGF-1 promotes mammary tumorigenesis in vivo have not been fully elucidated. To assess the possible involvement of COX-2 signaling in the pro-tumorigenic effe...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20868
更新日期:2012-12-01 00:00:00
abstract::PCPH is a gene involved in the regulation of eukaryotic cell proliferation and stress response. Recently, analyses of human and animal solid tumors and cell lines suggested that PCPH protein deregulation may participate in neoplastic progression. To test this possibility, we first examined PCPH expression in several l...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.10091
更新日期:2002-12-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Although AMPK is traditionally thought to play a major role in the regulation of cellular lipid and protein metabolism, recent discoveries reveal that AMPK inhibits mammalian target of rapamycin (mTOR) signaling and connec...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20793
更新日期:2012-03-01 00:00:00
abstract::We examined the expression of two groups of matrix metalloproteinases (MMPs), stromelysin and interstitial collagenase, in human skin cancer by northern blot analysis and in situ hybridization. Stromelysin-3 (ST-3) mRNA was overexpressed more than tenfold in 17 of 19 (89%) specimens of basal cell carcinoma (BCC) but i...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940090105
更新日期:1994-01-01 00:00:00
abstract::Telomerase expression is the hallmark of tumor cells, and activation of this ribonucleoprotein complex may be a rate-limiting or critical step in cellular immortalization and oncogenesis. Fungal immunomodulatory protein, FIP-gts, has been isolated from Ganoderma tsugae. In the present study, we expressed and purified ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20161
更新日期:2006-04-01 00:00:00
abstract::The tumor suppressor p27, which is a member of the Cip/Kip family of Cyclin-dependent kinase inhibitory proteins (CKIs), controls anti-proliferative events. The post-translational addition of O-GlcNAc to p27 occurs in HEK293T and HCC (hepatocellular carcinoma) cell lines, and we identified Ser2, Ser106, Ser110, Thr157...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22490
更新日期:2017-01-01 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::To study the possible involvement of DNA damage in cell transformation induced by estrogens, we examined whether DNA adduct formation is elicited in cultured Syrian hamster embryo (SHE) cells treated with estrogens and their derivatives by means of the 32P-postlabeling assay. Morphological transformation of the cells ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199607)16:3<149::AID-MC5>3
更新日期:1996-07-01 00:00:00
abstract::Nuclear factor kappa B (NFkappaB) is a central participant in the metastasis and chemoresistance of colorectal cancer (CRC). However, it is not fully understood to what extent NFkappaB contributes to induction of the metastasis-associated matrix metalloprotease-9 (MMP-9) gene and sensitivity to the commonly used chemo...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20288
更新日期:2007-05-01 00:00:00
abstract::Apc mutations cause intestinal tumorigenesis through Tcf4 activation. However, direct techniques for studying Tcf4 activation in vivo are limited. Here, we describe the development of a Tcf4-GFP reporter mouse model for directly studying Tcf4 activation. We first developed a GFP reporter construct (Tcf4-GFP) and trans...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20526
更新日期:2009-09-01 00:00:00
abstract::DPC4/SMAD4 is a candidate tumor suppressor gene with a strikingly high frequency of gene alterations in pancreatic cancer that suggests a discrete role for DPC4 in these tumors. DPC4 tumor-suppressive function has been implicated to mediate the transforming growth factor-beta (TGFbeta)-suppressive pathway; however, in...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199909)26:1<37::aid-mc5>3.
更新日期:1999-09-01 00:00:00
abstract::Environmental health science research, with its focus on fundamental science and disease prevention, is important for the development of rational and cost-effective public health and regulatory policies related to environmental protection. Environmentally related diseases are preventable, yet they impose a major burde...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章,评审
doi:10.1002/mc.2940140103
更新日期:1995-09-01 00:00:00
abstract::RhoBTB2 was isolated recently as a tumor suppressor gene from human chromosome 8p21.3. Although RhoBTB2 was found to be frequently lost in breast cancer lines, expression status of RhoBTB2 in sporadic breast cancer tissues and its clinical and prognostic value, however, remain unclear. Tissue samples from breast cance...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20598
更新日期:2010-03-01 00:00:00
abstract::In rats, gamma-glutamyl transpeptidase (gamma GT) exists as a single-copy gene, and three distinct species of RNA (types I, II, and III) that differ in their 5' untranslated regions have been identified. To compare steady-state levels of these gamma GT RNAs in rat tissues, hepatic carcinomas, and cultured cells, we us...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050112
更新日期:1992-01-01 00:00:00
abstract::The genetic or functional inactivation of the p53 pathway plays an important role with regards to disease progression from the chronic phase (CP) to blast phase (BP) and imatinib treatment response in chronic myeloid leukemia (CML). Two functional single nucleotide polymorphisms (SNPs), p53 R72P and MDM2 SNP309, are a...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22061
更新日期:2014-12-01 00:00:00
abstract::Tumor progression is a multistep process, which enables cells to evolve from benign to malignant tumors. This progression has been suggested to depend on six essential characteristics identified as the "hallmarks of cancer," which include: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals,...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20105
更新日期:2005-08-01 00:00:00
abstract::Although fibroblast growth factor (FGF) signals are strongly associated with malignancy, limited information is available regarding the role of the FGF9 signal in colorectal cancer (CRC). In this study, we investigated the frequency of FGF9 amplification in CRC clinical specimens and the association between the FGF9 g...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22476
更新日期:2017-01-01 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::Xiphophorus fish have been the subject of intensive genetic research for more than 60 yr, primarily because of the availability of a number of interspecific hybrids that are malignant melanoma models with apparently simple oncogene and tumor suppressor gene determinants. The gene map of Xiphophorus is one of the most ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199807)22:3<150::aid-mc2>3
更新日期:1998-07-01 00:00:00
abstract::Oncoprotein p28(GANK), overexpressed in hepatocellular carcinomas (HCC), binds to RelA and retains NF-κB in the cytoplasm to suppress NF-κB transactivation. However, the mechanism has not yet been elucidated. In this study, we clarified the mechanism of NF-κB regulated by p28(GANK). p28(GANK) reduced TNF-α-induced nuc...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22235
更新日期:2015-12-01 00:00:00
abstract::Potassium chromate induced the formation of DNA-protein complexes in cultured Chinese hamster ovary cells. The DNA-protein complexes were isolated by ultracentrifugal sedimentation in the presence of 2% sodium dodecyl sulfate (SDS) and 5 M urea. Two-dimensional SDS-polyacrylamide gel electrophoresis analysis of the ch...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010208
更新日期:1988-01-01 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::Although many anti-VEGF agents are available for cancer treatment, side effects of these agents limit their application for cancer treatment and prevention. Here we studied the potential use of a diet-based agent as an inhibitor for VEGF production. Using a VEGF reporter assay, our data showed that an extract from cin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22506
更新日期:2017-02-01 00:00:00
abstract::The atomic bombing of Hiroshima and Nagasaki and the nuclear accident at Chernobyl raised the question of prenatal sensitivity to ionizing radiation-induced cancer. In this study, mice were exposed to single doses of gamma-radiation (0.2-2.0 Gy) at different embryonic stages. The tumor incidence increased with dose fr...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::In this report we characterized the transcriptional regulation of the rat mdr1b gene by xenobiotics. The expression of this gene was increased in primary rat hepatocytes and in the H4-II-E hepatoma cell line by exposure to carcinogens such as aflatoxin B1, N-acetoxy-2-acetylaminofluorene, and methyl methanesulfonate. ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940130109
更新日期:1995-05-01 00:00:00
abstract::Cytokines are considered to play an important role in tumor pathogenesis and progression, and recent studies have demonstrated that a variety of forms, including interleukins (ILs) and transforming growth factor-beta(s) (TGF-beta(s)), may regulate tumors. In the present study, the expression of TGF-beta isoforms and I...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:
更新日期:2002-02-01 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