Abstract:
:The tumor-suppressor gene PTEN encodes a multifunctional phosphatase that is mutated in a variety of human cancers. PTEN inhibits the phosphatidylinositol 3-kinase pathway and downstream functions, including activation of Akt/protein kinase B (PKB), cell survival, and cell proliferation in tumor cells carrying mutant- or deletion-type PTEN. In such tumor cells, enforced expression of PTEN decreases cell proliferation through cell-cycle arrest at G1 phase accompanied, in some cases, by induction of apoptosis. More recently, the tumor-suppressive effect of PTEN has been reported in ovarian and thyroid tumors that are wild type for PTEN. In the present study, we examined the tumor-suppressive effect of PTEN in human colorectal cancer cells that are wild type for PTEN. Adenoviral-mediated transfer of PTEN (Ad-PTEN) suppressed cell growth and induced apoptosis significantly in colorectal cancer cells (DLD-1, HT29, and SW480) carrying wtPTEN than in normal colon fibroblast cells (CCD-18Co) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase (FAK) and mitogen-activated protein kinase (MAPK) and cell-cycle arrest at the G2/M phase, but not the G1 phase. Furthermore, treatment of human colorectal tumor xenografts (HT-29, and SW480) with Ad-PTEN resulted in significant (P=0.01) suppression of tumor growth. These results indicate that Ad-PTEN exerts its tumor-suppressive effect on colorectal cancer cells through inhibition of cell-cycle progression and induction of cell death. Thus Ad-PTEN may be a potential therapeutic for treatment of colorectal cancers.
journal_name
Gene Therjournal_title
Gene therapyauthors
Saito Y,Swanson X,Mhashilkar AM,Oida Y,Schrock R,Branch CD,Chada S,Zumstein L,Ramesh Rdoi
10.1038/sj.gt.3302100keywords:
subject
Has Abstractpub_date
2003-11-01 00:00:00pages
1961-9issue
23eissn
0969-7128issn
1476-5462pii
3302100journal_volume
10pub_type
杂志文章相关文献
GENE THERAPY文献大全abstract::Late pregnant rats exhibit endogenous opioid restraint of oxytocin cells since i.v. naloxone (NLX opioid antagonist) increases oxytocin (OXT) secretion but OXT nerve terminals become desensitised to opioids. We have studied central opioid inhibition of OXT neurones in late pregnancy by measuring SON OXT neurones firin...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and cha...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3303055
更新日期:2008-02-01 00:00:00
abstract::To test whether fast-acting, self-complimentary (sc), adeno-associated virus-mediated RPE65 expression prevents cone degeneration and/or restores cone function, we studied two mouse lines: the Rpe65-deficient rd12 mouse and the Rpe65-deficient, rhodopsin null ('that is, cone function-only') Rpe65(-/-)::Rho(-/-) mouse....
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2010.29
更新日期:2010-07-01 00:00:00
abstract::Adeno-associated virus (AAV)-mediated gene delivery systems have been shown to be effective tools for gene manipulation in the inner ear. For example, hair cells (HCs) and multiple other cell types can be transduced by the local injection of AAVs into the inner ear. However, application of the AAV-mediated CRISPR/Cas9...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/s41434-020-0124-1
更新日期:2020-08-01 00:00:00
abstract::A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte-macrophage colony-stimulat...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302275
更新日期:2004-07-01 00:00:00
abstract::We investigated the efficiency of activated polyamidoamine dendrimers, a new class of nonviral vectors, to transfect rabbit and human corneas in ex vivo culture. In addition to assessing the expression of a marker gene we have demonstrated that this approach can be used to induce the production of TNF receptor fusion ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300886
更新日期:1999-05-01 00:00:00
abstract::Genetic modification of tumor cells with the gene for the B7.1 or with the genes for cytokines results in increased tumor cell immunogenicity. In the work reported here, immunization of naive animals with either B7.1 or gamma-IFN gene-modified MCA106 tumor cells effectively protects the host from subsequent challenge ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300820
更新日期:1999-02-01 00:00:00
abstract::Coagulation factor X (FX)-binding ablated adenovirus type 5 (Ad5) vectors have been genetically engineered to ablate the interaction with FX, resulting in substantially reduced hepatocyte transduction following intravenous administration in rodents. Here, we quantify viral genomes and gene transfer mediated by Ad5 and...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2011.87
更新日期:2012-01-01 00:00:00
abstract::Transplantation faces several major obstacles that could be overcome by expression of immunomodulatory proteins through application of gene therapy techniques. Gene therapy strategies to prolong graft survival involve gene transfer of immunosuppressive or graft-protecting molecules. Very promising results have been ob...
journal_title:Gene therapy
pub_type: 杂志文章,评审
doi:10.1038/sj.gt.3301083
更新日期:2000-01-01 00:00:00
abstract::Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhib...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2012.42
更新日期:2013-03-01 00:00:00
abstract::Gene therapy is a potential new strategy for the treatment of cardiovascular disease. The most efficacious method of gene delivery remains a key hurdle to effective gene therapy. We present the application of a novel, nonviral gene delivery system (TerplexDNA) to augment myocardial transfection. The hearts of New Zeal...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301395
更新日期:2001-03-01 00:00:00
abstract::Hypoxia initiates an adaptive physiological response in all organisms and plays a role in the pathogenesis of several human diseases. The hypoxia/HIF-inducible factor-1 (HIF-1) transcription factor mediates transcriptional responses to hypoxia by binding to a cis-acting hypoxia-responsive element (HRE) present within ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301605
更新日期:2001-12-01 00:00:00
abstract::Viral gene vectors often rely on packaging cell lines, which provide the necessary factors in trans for the formation of virus-like particles. Previously, we reported on a first-generation packaging cell line for gene vectors, which are based on the B-lymphotropic Epstein-Barr virus (EBV), a human gamma-herpesvirus. T...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302714
更新日期:2006-05-01 00:00:00
abstract::For successful cancer gene therapy via intravenous (i.v.) administration, it is essential to optimize the stability of carriers in the systemic circulation and the cellular association after the accumulation of the carrier in tumor tissue. However, a dilemma exists regarding the use of poly(ethylene glycol) (PEG), whi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302843
更新日期:2007-01-01 00:00:00
abstract::Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leadin...
journal_title:Gene therapy
pub_type: 信件,评审
doi:10.1038/s41434-018-0004-0
更新日期:2018-04-01 00:00:00
abstract::Citrullinemia type 1 (CTLN1) is an autosomal recessive disorder of metabolism caused by a deficiency of argininosuccinate synthetase. Despite optimal management, CTLN1 patients still suffer from lethal metabolic instability and experience life-threatening episodes of acute hyperammonemia. A murine model of CTLN1 (fold...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2013.53
更新日期:2013-12-01 00:00:00
abstract::Replication defective viral vectors provide a potentially useful means of gene transfer to oligodendrocytes and thus for studying the pathogenesis of white matter disease. In this study we have examined the expression pattern of E1/E3 deleted adenoviral vectors expressing the reporter gene LacZ (AdlacZ) as a means of ...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300971
更新日期:1999-08-01 00:00:00
abstract::Alphavirus vectors based on Sindbis virus and Semliki Forest virus (SFV) were characterized as potential gene transfer vectors. Initial studies were performed using vectors engineered to transfer either lacZ or green fluorescent protein (GFP). High levels of gene transfer were achieved in human primary fibroblasts, BH...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301122
更新日期:2000-03-01 00:00:00
abstract::Complexes of DNA and cationic lipid offer potential advantages for gene transfer to airway epithelia. However, we found that application of DNA-lipid (DMRIE-DOPE) complexes to primary cultures of human ciliated airway epithelia or explants of rabbit trachea generated only low levels of gene transfer. In contrast, when...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300524
更新日期:1997-11-01 00:00:00
abstract::The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this re...
journal_title:Gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::To facilitate the understanding of the complex process of target gene expression and its control, we report a modified inducible system for activation or repression of target gene expression in response to an exogenously administered compound. The main component of this inducible system is a chimeric transcriptional a...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300402
更新日期:1997-05-01 00:00:00
abstract::For the development of human immunodeficiency virus type 1 (HIV-1) vaccines, traditional approaches inducing virus-neutralizing antibodies have so far failed. Thus the effort is now focused on elicitation of cellular immunity. We are currently testing in clinical trials in the United Kingdom and East Africa a T-cell v...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302241
更新日期:2004-07-01 00:00:00
abstract::There is currently an urgent need to develop efficient gene-delivery systems for the lung that are free of inflammatory effects. The LID vector is a synthetic gene delivery system, comprised of lipofectin (L), an integrin-targeting peptide (I) and DNA (D) that has previously been shown to have high transfection effici...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301963
更新日期:2003-06-01 00:00:00
abstract::Hepatic sequestration of systemically administered adenoviral vectors reduces the number of viral particles available for delivery to other tissues. The biological basis of this phenomenon was investigated using a new in vivo technique which permitted imaging in real time. Recombinant adenovirus serotype 5 knob (Ad5K)...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3300659
更新日期:1998-06-01 00:00:00
abstract::The canine is the most important large animal model for testing novel hemophilia A (HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, different biological properties between cFVIII and human FVIII (hFVIII) indicated t...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2016.34
更新日期:2016-07-01 00:00:00
abstract::Many retroviral vectors based on murine leukaemia virus (MLV) contain the first 420 nucleotides of the gag gene, as this was reported to increase vector titre by increasing the efficiency of RNA packaging. In this study, deletion of this gag sequence from its original location did not decrease the titre of two retrovi...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301081
更新日期:2000-02-01 00:00:00
abstract::Defensins are small cationic proteins that harbor broad-spectrum microbicidal activity against bacteria, fungi and viruses. This study examines the effects on pathogens of the epidermis engineered to express human beta-defensin 3 (HBD3) to combat bacterial infections. First, we examined the localization of HBD3 in the...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302472
更新日期:2005-05-01 00:00:00
abstract::We recently showed that the human telomerase reverse transcriptase (hTERT) promoter induces tumor-specific Bax gene expression and selectively kills various human cancer cells both in vitro and in xenograft tumors. However, it remains unclear whether the hTERT promoter can be used to induce transgene expression in syn...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3301619
更新日期:2002-01-01 00:00:00
abstract::Hyperammonemia is less severe in arginase 1 deficiency compared with other urea cycle defects. Affected patients manifest hyperargininemia and infrequent episodes of hyperammonemia. Patients typically suffer from neurological impairment with cortical and pyramidal tract deterioration, spasticity, loss of ambulation, s...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/gt.2014.106
更新日期:2015-02-01 00:00:00
abstract::In high-risk patients, the ideal cardiovascular gene therapy requires a strategy that provides long-term protection of myocardium against episodes of ischemic/reperfusion injury. We report the development of an efficient, long-lasting pre-emptive gene therapy strategy in a rat model of ischemic-reperfusion (I/R) injur...
journal_title:Gene therapy
pub_type: 杂志文章
doi:10.1038/sj.gt.3302250
更新日期:2004-06-01 00:00:00