Transcriptionally mediated inhibition of telomerase of fungal immunomodulatory protein from Ganoderma tsugae in A549 human lung adenocarcinoma cell line.

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 the recombinant fungal immunomodulatory protein reFIP-gts in E. coli. We found that reFIP-gts significantly and selectively inhibits the growth of A549 cancer cells while not affecting the growth of normal MRC-5 fibroblasts. The reFIP-gts suppression of telomerase activity is concentration-dependent, due to the downregulation of the telomerase catalytic subunit (hTERT). It also happens at the mRNA level. These results were confirmed by transient transfections of A549 cells with pGL3-Basic plasmid constructs containing the functional hTERT promoter and its E-box-deleted sequences cloned upstream of a luciferase reporter gene. With electrophoretic mobility shift assays and Western blotting, we demonstrated that in response to reFIP-gts, binding of c-myc transcriptional factor to the E-box sequence on the hTERT promoter is inhibited. These results show that reFIP-gts suppresses telomerase activity and inhibits transcriptional regulation of hTERT via a c-myc-responsive element-dependent mechanism. Our findings provide new insight into both the anticancer function of reFIP-gts and the regulation of hTERT/telomerase expression, which may be valuable in the development of a promising chemopreventive agent.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Liao CH,Hsiao YM,Hsu CP,Lin MY,Wang JC,Huang YL,Ko JL

doi

10.1002/mc.20161

subject

Has Abstract

pub_date

2006-04-01 00:00:00

pages

220-9

issue

4

eissn

0899-1987

issn

1098-2744

journal_volume

45

pub_type

杂志文章
  • Cellular ubiquitination and proteasomal functions positively modulate mammalian nucleotide excision repair.

    abstract::The ubiquitin-proteasome pathway is fundamental to synchronized continuation of many cellular processes, for example, cell-cycle progression, stress response, and cell differentiation. Recent studies have shown that the ubiquitin-proteasome pathway functions in the regulation of nucleotide excision repair (NER) in yea...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20065

    authors: Wang QE,Wani MA,Chen J,Zhu Q,Wani G,El-Mahdy MA,Wani AA

    更新日期:2005-01-01 00:00:00

  • Mapping of tyrosine kinase gene family members in a Xiphophorus melanoma model.

    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

    authors: Morizot DC,McEntire BB,Della Coletta L,Kazianis S,Schartl M,Nairn RS

    更新日期:1998-07-01 00:00:00

  • Pre-existing Fas ligand (FasL) in cancer cells elicits tumor-specific protective immunity, but delayed induction of FasL expression after inoculation facilitates tumor formation.

    abstract::Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL-expressing tumors may counterattack tumor-infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape. In order to distin...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21909

    authors: Chiu HY,Sun GH,Chen SY,Wang HH,Ho MY,Chu CY,Wu WL,Jhou RS,Tsai YL,Huang RT,Sun KH,Tang SJ

    更新日期:2013-09-01 00:00:00

  • Formation of an active form of the interleukin-2/15 receptor beta-chain by insertion of the intracisternal A particle in a radiation-induced mouse thymic lymphoma and its role in tumorigenesis.

    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-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10128

    authors: Ukai H,Ishii-Oba H,Ukai-Tadenuma M,Ogiu T,Tsuji H

    更新日期:2003-06-01 00:00:00

  • Overexpression of a constitutively active form of c-src in skin epidermis increases sensitivity to tumor promotion by 12-O-tetradecanoylphorbol-13-acetate.

    abstract::Transgenic mice were developed to study the role of c-src in epithelial tumorigenesis through targeted expression of a constitutively active form of murine c-src (src(529)). Src(529) was targeted to the interfollicular epidermis with the human keratin 1 (HK1) promoter. The skin phenotype of these mice was characterize...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10030

    authors: Matsumoto T,Jiang J,Kiguchi K,Carbajal S,Rho O,Gimenez-Conti I,Beltrán L,DiGiovanni J

    更新日期:2002-03-01 00:00:00

  • Aberrant expression and localization of connexin43 and connexin30 in a rat glioma cell line.

    abstract::Gap junctions are cellular structures which permit direct exchanges of small molecules from cytoplasm to cytoplasm in most of the cells of metazoan organisms. For four decades, it has been observed that the inhibition of this type of intercellular communication is often associated with tumorigenesis. The assumption th...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20393

    authors: Mennecier G,Derangeon M,Coronas V,Hervé JC,Mesnil M

    更新日期:2008-05-01 00:00:00

  • Methanol exposure does not lead to accumulation of oxidative DNA damage in bone marrow and spleen of mice, rabbits or primates.

    abstract::Genotoxicity tests indicate methanol (MeOH) is not mutagenic, but a rodent study has suggested carcinogenic potential, which could result from free radical-initiated oxidative DNA damage. To investigate this possibility we treated male CD-1 mice, New Zealand white rabbits, and cynomolgus monkeys with MeOH (2.0 g/kg ip...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20701

    authors: McCallum GP,Siu M,Ondovcik SL,Sweeting JN,Wells PG

    更新日期:2011-03-01 00:00:00

  • The same gamma-glutamyl transpeptidase RNA species is expressed in fetal liver, hepatic carcinomas, and rasT24-transformed rat liver epithelial cells.

    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

    authors: Habib GM,Rajagopalan S,Godwin AK,Lebovitz RM,Lieberman MW

    更新日期:1992-01-01 00:00:00

  • Dys-regulation of clusterin in human hepatoma is not associated with tumorigenesis but is secondary to cell response to external tresses.

    abstract::It becomes feasible to perform genome-wide differential gene or protein expression in the post genome era. However, little has been addressed on the effects of external stresses and microenvironment alterations on the outcomes of gene and protein expression. To identify downregulated genes during hepatoma development,...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20095

    authors: Hsieh SY,Chen WY,Shih TC,Yeh JY,Jeng JT

    更新日期:2005-06-01 00:00:00

  • Infrequent loss of heterozygosity and mutation of the p53 gene in immortal and transformed mouse embryo fibroblasts.

    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

    authors: Tokumitsu M,Kadohama T,Ogawa K

    更新日期:1994-05-01 00:00:00

  • Alterations in RD(INK4/ARF) -mediated en bloc regulation of the INK4-ARF locus in human squamous cell carcinoma of the head and neck.

    abstract::The presence of RD(INK4/ARF) (RD) enhancer in the INK4-ARF locus provides a novel mechanism to simultaneously increase the transcription of p15(INK4b) (p15), p14ARF (p14), and p16(INK4a) (p16). While such upregulation can be repressed through interactions between RD and oncoproteins CDC6 and BMI1, little is known abou...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22119

    authors: Poi MJ,Knobloch TJ,Sears MT,Warner BM,Uhrig LK,Weghorst CM,Li J

    更新日期:2015-07-01 00:00:00

  • The effect of the JE (MCP-1) gene, which encodes monocyte chemoattractant protein-1, on the growth of HeLa cells and derived somatic-cell hybrids in nude mice.

    abstract::To investigate the effect of tumor-associated macrophages on the in vivo growth properties of cervical carcinoma cells, tumorigenic human papilloma virus (HPV) 18-positive HeLa cells were transfected with an expression vector harboring the cDNA for the macrophage chemoattractant protein-1 JE (MCP-1). Although the endo...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940140307

    authors: Kleine K,König G,Kreuzer J,Komitowski D,Zur Hausen H,Rösl F

    更新日期:1995-11-01 00:00:00

  • Polymorphisms in GSTM1 and XPD genes predict clinical outcome in advanced oral cancer patients treated with postoperative radiotherapy.

    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

    authors: Mahimkar MB,Samant TA,Kannan S,Tulsulkar J,Pai PS,Anantharaman D

    更新日期:2012-10-01 00:00:00

  • Downregulation of STAT3/NF-κB potentiates gemcitabine activity in pancreatic cancer cells.

    abstract::There is an unmet need to develop new agents or strategies against therapy resistant pancreatic cancer (PanCA). Recent studies from our laboratory showed that STAT3 negatively regulates NF-κB and that inhibition of this crosstalk using Nexrutine® (Nx) reduces transcriptional activity of COX-2. Inhibition of these mole...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22503

    authors: Gong J,Muñoz AR,Pingali S,Payton-Stewart F,Chan DE,Freeman JW,Ghosh R,Kumar AP

    更新日期:2017-02-01 00:00:00

  • Potent cell growth inhibitory effects in hepatitis B virus X protein positive hepatocellular carcinoma cells by the selective cyclooxygenase-2 inhibitor celecoxib.

    abstract::Hepatitis B virus (HBV) X protein (HBx) and cyclooxygenase-2 (COX-2) are all playing roles in hepatocellular carcinoma (HCC), but the reversing effects of COX-2 inhibitors on the neoplastic features caused by HBx protein is still unclear. To further evaluate the therapeutic potential of celecoxib on HBx mediated trans...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20455

    authors: Xie H,Gao L,Chai N,Song J,Wang J,Song Z,Chen C,Pan Y,Zhao L,Sun S,Wu K,Feitelson MA,Liu J,Fan D

    更新日期:2009-01-01 00:00:00

  • Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

    abstract::Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associate...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22763

    authors: Rossi EL,Khatib SA,Doerstling SS,Bowers LW,Pruski M,Ford NA,Glickman RD,Niu M,Yang P,Cui Z,DiGiovanni J,Hursting SD

    更新日期:2018-03-01 00:00:00

  • Microarray meta-analysis defines global angiogenesis-related gene expression signatures in human carcinomas.

    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

    authors: Anders M,Fehlker M,Wang Q,Wissmann C,Pilarsky C,Kemmner W,Höcker M

    更新日期:2013-01-01 00:00:00

  • Cdkn2a encodes functional variation of p16INK4a but not p19ARF, which confers selection in mouse lung tumorigenesis.

    abstract::The cyclin-dependent kinase inhibitor 2a (Cdkn2a) locus encodes two distinct tumor suppressors, p16INK4a and p19ARF, whose functions interrelate in the regulation of cell proliferation as key components of the retinoblastoma and p53 pathways, respectively. In many types of cancer, alterations of Cdkn2a abrogate the fu...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199906)25:2<92::aid-mc3>3.

    authors: Herzog CR,Noh S,Lantry LE,Guan KL,You M

    更新日期:1999-06-01 00:00:00

  • Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma.

    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

    authors: Lin J,Hou Y,Huang S,Wang Z,Sun C,Wang Z,He X,Tam NL,Wu C,Wu L

    更新日期:2019-02-01 00:00:00

  • Induction of glutathione s-transferase-pi in Barrett's metaplasia and Barrett's adenocarcinoma cell lines.

    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

    authors: Compton KR,Orringer MB,Beer DG

    更新日期:1999-02-01 00:00:00

  • Epigenetic regulation of the human ATP2A3 gene promoter in gastric and colon cancer cell lines.

    abstract::The knowledge about the role of calcium-regulated pathways in cancer cell growth and differentiation could be useful for the development of new therapeutic approaches to diminish its mortality. The ATP2A genes encode for SERCA pumps, which modulate cytosolic Ca2+ concentration, regulating various cellular processes in...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22978

    authors: Meneses-Morales I,Izquierdo-Torres E,Flores-Peredo L,Rodríguez G,Hernández-Oliveras A,Zarain-Herzberg Á

    更新日期:2019-06-01 00:00:00

  • Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis.

    abstract::Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue-specific manner. The Cre-loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5-Cre recombinase (K5Cre) transgenic mou...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20192

    authors: Chan EL,Peace BE,Toney K,Kader SA,Pathrose P,Collins MH,Waltz SE

    更新日期:2007-01-01 00:00:00

  • Targeting ERK beyond the boundaries of the kinase active site in melanoma.

    abstract::Extracellular signal-regulated kinase 1/2 (ERK1/2) constitute a point of convergence for complex signaling events that regulate essential cellular processes, including proliferation and survival. As such, dysregulation of the ERK signaling pathway is prevalent in many cancers. In the case of BRAF-V600E mutant melanoma...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1002/mc.23047

    authors: Sammons RM,Ghose R,Tsai KY,Dalby KN

    更新日期:2019-09-01 00:00:00

  • Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells.

    abstract::Dietary heterocyclic aromatic amines (HCA) and polyunsaturated fatty acids (PUFA) are both believed to play a role in colon carcinogenesis, and are both substrate for the enzyme cyclooxygenase (COX). In HCA-7 cells, highly expressing isoform COX-2, we investigated the effects of PUFA on prostaglandin synthesis and DNA...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20032

    authors: Moonen HJ,Dommels YE,van Zwam M,van Herwijnen MH,Kleinjans JC,Alink GM,de Kok TM

    更新日期:2004-07-01 00:00:00

  • Polyoma DNA replication dependent upon growth condition of SEWA sarcoma cells.

    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

    authors: Robinson R,Ronai Z

    更新日期:1990-01-01 00:00:00

  • Influence of the metabolic syndrome on leptin and leptin receptor in breast cancer.

    abstract::Obesity and its associated metabolic syndrome (MetS) are recognized risk factors for breast cancer. The molecular basis for this association remains largely unknown. Adipokines, in particular leptin and adiponectin, are thought to form part of the mechanism linking obesity with cancer through their altered expression/...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20764

    authors: Carroll PA,Healy L,Lysaght J,Boyle T,Reynolds JV,Kennedy MJ,Pidgeon G,Connolly EM

    更新日期:2011-08-01 00:00:00

  • Oxidative DNA damage causes premature senescence in mouse embryonic fibroblasts deficient for Krüppel-like factor 4.

    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

    authors: Liu C,La Rosa S,Hagos EG

    更新日期:2015-09-01 00:00:00

  • The Ron receptor tyrosine kinase is not required for adenoma formation in Apc(Min/+) mice.

    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

    authors: Meyer SE,Waltz SE,Goss KH

    更新日期:2009-11-01 00:00:00

  • Modulation of the oncogenic potential of beta-catenin by the subcellular distribution of plakoglobin.

    abstract::Plakoglobin (Pg) and beta-catenin are homologous proteins that function in cell-cell adhesion and signaling. The cadherin-associated form of these proteins mediates adhesion, whereas the cytosolic/nuclear form has a signaling role. Despite their interactions with common cellular partners, beta-catenin has a well-docum...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20310

    authors: Li L,Chapman K,Hu X,Wong A,Pasdar M

    更新日期:2007-10-01 00:00:00

  • Dishevelled-3 activates p65 to upregulate p120-catenin transcription via a p38-dependent pathway in non-small cell lung cancer.

    abstract::Dishevelled-3 (Dvl-3) and p120-catenin (p120ctn) have abnormal expression in non-small cell lung cancer (NSCLC), which is associated with poor prognosis. Dvl-3 upregulates p120ctn transcription in NSCLC cells, but the mechanism is unknown. Here we transiently transfected Dvl-3 cDNA to NSCLC cells. Dvl-3 transfection i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22196

    authors: Zhao H,Zhao Y,Jiang G,Zhang X,Zhang Y,Dong Q,Luan L,Papavassiliou P,Wang E,Wang E

    更新日期:2015-06-01 00:00:00