Resistance to apoptosis in human cells conferred by telomerase function and telomere stability.

Abstract:

:Cell senescence and programmed cell death (apoptosis) are two fundamental biological mechanisms that regulate proliferative capacity, survival potential, aging, and death of cells. Here we report several independent lines of experimental evidence that support the hypothesis that telomerase function and telomere length perform important roles in cell survival during apoptosis. First, with serum starvation and matrix-independent survival experiments, we found that young normal diploid cells were more resistant to apoptosis than their older counterparts. In addition, normal cells with stable telomere lengths caused by ectopic expression of telomerase maintained an increased resistance to serum starvation- and matrix-deprivation-induced programmed cell death compared with aged normal cells without telomerase. Second, we found that telomerase-positive immortalized SW39 cells had a higher survival ability and resistance to apoptosis than their telomerase-negative immortalized counterparts, SW13 and SW26. Third, we showed that telomerase-positive cells with experimentally elongated telomeres (GTR-IDH4 and GTR-DU145) acquired increased survival ability and higher resistance to apoptosis than the parental cell lines with shorter telomeres (IDH4 and DU145). Higher resistance to apoptosis of these cells was associated with a deficiency in two major apoptosis execution pathways: induction of nuclear calcium-dependent endonucleases and activation of the interleukin-1 beta-converting enzyme-family of proteases (caspases). Taken together, these results provide the first direct experimental evidence supporting the hypothesis that telomerase activity and maintenance of telomere stability are associated with increased cellular resistance to apoptosis.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Holt SE,Glinsky VV,Ivanova AB,Glinsky GV

subject

Has Abstract

pub_date

1999-08-01 00:00:00

pages

241-8

issue

4

eissn

0899-1987

issn

1098-2744

pii

10.1002/(SICI)1098-2744(199908)25:4<241::AID-MC2>3

journal_volume

25

pub_type

杂志文章
  • Overexpression of SHCBP1 promotes migration and invasion in gliomas by activating the NF-κB signaling pathway.

    abstract::Gliomas are common, aggressive central nervous system tumors with poor overall survival rates. Despite improvements in neurosurgery, chemotherapy, and radiotherapy, the outcomes of patients with malignant gliomas remain poor. Therefore, increased knowledge of the molecular mechanisms that regulate glioma progression i...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22834

    authors: Zhou Y,Tan Z,Chen K,Wu W,Zhu J,Wu G,Cao L,Zhang X,Zeng X,Li J,Zhang W

    更新日期:2018-09-01 00:00:00

  • Differential expression of cytokines in rat osteosarcoma and malignant fibrous histiocytoma cell lines induced by 4-(hydroxyamino)quinoline-1-oxide.

    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:

    authors: Honoki K,Tsujiuchi T,Sasaki Y,Tsutsumi M,Morishita T,Kido A,Miyauchi Y,Mii Y,Takakura Y,Konishi Y

    更新日期:2002-02-01 00:00:00

  • No involvement of Ki-ras or p53 gene mutations in colitis-associated rat colon tumors induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate.

    abstract::1-Hydroxyanthraquinone (1-HA), which is present in some herbs, and methylazoxymethanol (MAM) acetate, a metabolite of azoxymethane, show synergistic carcinogenicity in rat colon, and 1-HA induces ulcerative changes with simultaneous severe inflammation of the entire colon. In this study, mutations in Ki-ras (exons 1 a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940120403

    authors: Suzui M,Yoshimi N,Ushijima T,Hirose Y,Makita H,Wang A,Kawamori T,Tanaka T,Mori H,Nagao M

    更新日期:1995-04-01 00:00:00

  • Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53-mediated apoptosis in LNCaP prostate cancer cells.

    abstract::Previous studies have established the in vivo bioavailability and efficacious dosages of phenylbutyl isoselenocyanate (ISC-4), a selenium-substituted isothiocyanate, against mouse xenograft models of human melanoma and colorectal cancer. To explore its potential attributes against prostate cancer, we treated human LNC...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22825

    authors: Wu W,Karelia D,Pramanik K,Amin SG,Sharma AK,Jiang C,Lu J

    更新日期:2018-08-01 00:00:00

  • Susceptibility of transgenic mice carrying human prototype c-Ha-ras gene in a short-term carcinogenicity study of vinyl carbamate and ras gene analyses of the induced tumors.

    abstract::To determine if hemizygous transgenic mice carrying the human c-Ha-ras gene (CB6F1-Tg Hras2 mice (Hras2 mice)) are susceptible to the carcinogenic potential of known murine carcinogens, male and female Hras2 mice and their non-transgenic CB6F1 littermates (non-Tg mice) were each given a single intraperitoneal injectio...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3

    authors: Mitsumori K,Wakana S,Yamamoto S,Kodama Y,Yasuhara K,Nomura T,Hayashi Y,Maronpot RR

    更新日期:1997-11-01 00:00:00

  • Ras-mediated intestinal epithelial cell transformation requires cyclooxygenase-2-induced prostaglandin E2 signaling.

    abstract::Ras-mediated transformation is associated with upregulation of cyclooxygenase-2 (COX-2), which in turn promotes prostaglandin E2 (PGE2) synthesis and secretion. Although recent studies have identified molecular mechanisms by which Ras mediates upregulation of COX-2, conflicting observations have been made. Furthermore...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20333

    authors: Repasky GA,Zhou Y,Morita S,Der CJ

    更新日期:2007-12-01 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

  • Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma.

    abstract::In epithelial ovarian cancer, tumor grade is an independent prognosticator whose molecular determinants remain unknown. We investigated patterns of gene expression in well- and poorly differentiated serous papillary ovarian and peritoneal carcinomas with cDNA microarrays. A 6500-feature cDNA microarray was used for co...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10098

    authors: Jazaeri AA,Lu K,Schmandt R,Harris CP,Rao PH,Sotiriou C,Chandramouli GV,Gershenson DM,Liu ET

    更新日期:2003-02-01 00:00:00

  • p28(GANK) associates with p300 to attenuate the acetylation of RelA.

    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

    authors: Ren YB,Luo T,Li J,Fu J,Wang Q,Cao GW,Chen Y,Wang HY

    更新日期:2015-12-01 00:00:00

  • Transcriptional upregulation of MT2-MMP in response to hypoxia is promoted by HIF-1α in cancer cells.

    abstract::Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia-inducible factor-1α (HIF-1α) through coordinated regulation of hypoxia-responsive genes. In this study, we found that m...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20678

    authors: Zhu S,Zhou Y,Wang L,Zhang J,Wu H,Xiong J,Zhang J,Tian Y,Wang C,Wu H

    更新日期:2011-10-01 00:00:00

  • Matrix metalloproteinase3 gene promoter polymorphisms and their haplotypes are associated with gastric cancer risk in eastern Indian population.

    abstract::Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase3 (MMP3) promoter in the development and progression of gastric cancer of whole stomach has never been investigated in any population. We conducted a hospital-based case-control study to explore the MMP3 SNPs and their haplotypes with the risk of gastri...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21837

    authors: Dey S,Stalin S,Gupta A,Saha D,Kesh K,Swarnakar S

    更新日期:2012-10-01 00:00:00

  • SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling.

    abstract::Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell ca...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.23246

    authors: Chen L,Xie Y,Ma X,Zhang Y,Li X,Zhang F,Gao Y,Fan Y,Gu L,Wang L,Zhang X,Fu B

    更新日期:2020-10-01 00:00:00

  • Dipyridamole intervention of breast cell carcinogenesis.

    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

    authors: Choudhary S,Sood S,Wang HC

    更新日期:2014-03-01 00:00:00

  • Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy.

    abstract::Cancer cells mainly rely on glycolysis for energetic needs, and mitochondrial ATP production is almost inactive. However, cancer cells require the integrity of mitochondrial functions for their survival, such as the maintenance of the internal membrane potential gradient (DeltaPsim). It thus may be predicted that Delt...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20539

    authors: Loiseau D,Morvan D,Chevrollier A,Demidem A,Douay O,Reynier P,Stepien G

    更新日期:2009-08-01 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

  • Possible involvement of c-myc but not ras genes in hepatocellular carcinomas developing after spontaneous hepatitis in LEC rats.

    abstract::LEC (Long-Evans with a cinnamon-like coat color) rats develop hepatocellular carcinomas (HCCs) spontaneously. We examined mutations of codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes in four HCCs by the polymerase chain reaction (PCR)-single-stranded DNA direct sequencing method. No ras gene mutations wer...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940040405

    authors: Fujimoto Y,Ishizaka Y,Tahira T,Sone H,Takahashi H,Enomoto K,Mori M,Sugimura T,Nagao M

    更新日期:1991-01-01 00:00:00

  • Tocopherols inhibit oxidative and nitrosative stress in estrogen-induced early mammary hyperplasia in ACI rats.

    abstract::Oxidative stress is known to play a key role in estrogen-induced breast cancer. This study assessed the chemopreventive activity of the naturally occurring γ-tocopherol-rich mixture of tocopherols (γ-TmT) in early stages of estrogen-induced mammary hyperplasia in ACI rats. ACI rats provide an established model of rode...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22164

    authors: Das Gupta S,So JY,Wall B,Wahler J,Smolarek AK,Sae-Tan S,Soewono KY,Yu H,Lee MJ,Thomas PE,Yang CS,Suh N

    更新日期:2015-09-01 00:00:00

  • The enhancing effects of obesity on mammary tumor growth and Akt/mTOR pathway activation persist after weight loss and are reversed by RAD001.

    abstract::The prevalence of obesity, an established risk and progression factor for postmenopausal breast cancer, remains high in US women. Activation of Akt/mammalian target of rapamycin (mTOR) signaling plays a key role in the obesity-breast cancer link. However, the impact of weight normalization in obese postmenopausal wome...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.21878

    authors: De Angel RE,Conti CJ,Wheatley KE,Brenner AJ,Otto G,Degraffenried LA,Hursting SD

    更新日期:2013-06-01 00:00:00

  • Aurora B kinase as a novel molecular target for inhibition the growth of osteosarcoma.

    abstract::Osteosarcoma is the primary human malignant tumor affecting bone. This cancer most frequently arises in children and adolescents, with a second peak in those over the age of 50. Currently, surgery followed by radiotherapy and chemotherapy are the main treatments, but long-term positive effects are very poor. Aurora B ...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22993

    authors: Zhao Z,Jin G,Yao K,Liu K,Liu F,Chen H,Wang K,Gorja DR,Reddy K,Bode AM,Guo Z,Dong Z

    更新日期:2019-06-01 00:00:00

  • Reduction in tamoxifen-induced CYP3A2 expression and DNA adducts using antisense technology.

    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

    authors: Mahadevan B,Arora V,Schild LJ,Keshava C,Cate ML,Iversen PL,Poirier MC,Weston A,Pereira C,Baird WM

    更新日期:2006-02-01 00:00:00

  • Induction of karyotype instability in a murine tumor cell line by quercetin, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine, and okadaic acid, as revealed by transmission distortion of the inactive X chromosome.

    abstract::Quercetin, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter-like activity. The effects of these three compounds on the transmission of the inactive X chromosome were examined in MST-C6 murine tumor cells, which were de...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.2940140411

    authors: Kuwabara K,Odani S,Takahashi Y,Arakawa M,Takagi N,Nagao M,Kominami R

    更新日期:1995-12-01 00:00:00

  • A comparative analysis of allelic imbalance events in chemically induced rat mammary, colon, and bladder tumors.

    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.

    authors: Haag JD,Brasic GM,Shepel LA,Newton MA,Grubbs CJ,Lubet RA,Kelloff GJ,Gould MN

    更新日期:1999-01-01 00:00:00

  • Activation and up-regulation of translation initiation factor 4B contribute to arsenic-induced transformation.

    abstract::Arsenic is a known human carcinogen. However, the mechanism of how arsenic induces cell transformation remains unclear. In this study, we demonstrated that long-term exposure to sodium arsenite at low-dose (2 µM) increases cell proliferation and neoplastic transformation in a mouse epidermal cell model, JB6 promotion-...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20733

    authors: Zhang Y,Wang Q,Guo X,Miller R,Guo Y,Yang HS

    更新日期:2011-07-01 00:00:00

  • Growth factor-independent proliferation of rat mammary carcinoma cells by autocrine secretion of neu-differentiation factor/heregulin and transforming growth factor-alpha.

    abstract::Serially transplantable rat mammary tumor (RMT) cells are not dependent on exogenous epidermal growth factor (EGF) and insulin-like growth factor-I for continuous growth in serum-free medium. Previously, we found that conditioned medium obtained from these cells contained EGF-like mitogenic activity and stimulated tyr...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/(SICI)1098-2744(199602)15:2<134::AID-MC6>3

    authors: Ethier SP,Langton BC,Dilts CA

    更新日期:1996-02-01 00:00:00

  • Cinnamon extract reduces VEGF expression via suppressing HIF-1α gene expression and inhibits tumor growth in mice.

    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

    authors: Zhang K,Han ES,Dellinger TH,Lu J,Nam S,Anderson RA,Yim JH,Wen W

    更新日期:2017-02-01 00:00:00

  • Involvement of the Akt/mTOR pathway on EGF-induced cell transformation.

    abstract::Our previous study demonstrated that phosphatidylinositol 3-kinase (PI3K) is necessary for epidermal growth factor (EGF)-induced cell transformation in mouse epidermal JB6 cells. Akt and the mammalian target of rapamycin (mTOR) are regarded as PI3K downstream effectors. Therefore, in this study, we investigated the ro...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.10140

    authors: Nomura M,He Z,Koyama I,Ma WY,Miyamoto K,Dong Z

    更新日期:2003-09-01 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

  • Reduced expression of the Rassf1a gene and its aberrant DNA methylation in pancreatic duct adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

    abstract::Alterations of the Rassf1a gene were investigated in pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters. Female Syrian golden hamsters received 70 mg/kg BOP, followed by repeated exposures to an augmentation pressure regimen consisting of a choline-deficient diet combine...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.20250

    authors: Shimizu K,Itsuzaki Y,Fujii H,Honoki K,Tsujiuchi T

    更新日期:2008-02-01 00:00:00

  • No difference in 4-nitroquinoline induced tumorigenesis between germ-free and colonized mice.

    abstract::Variations in oral bacterial communities have been linked to oral cancer suggesting that the oral microbiome is an etiological factor that can influence oral cancer development. The 4-nitroquinoline 1-oxide (4-NQO)-induced murine oral and esophageal cancer model is frequently used to assess the effects of preventive a...

    journal_title:Molecular carcinogenesis

    pub_type: 杂志文章

    doi:10.1002/mc.22972

    authors: Zhou YX,Fuentes-Creollo G,Ponce F,Langley SA,Jen KY,Celniker SE,Mao JH,Snijders AM

    更新日期:2019-05-01 00:00:00

  • A superoxide anion generator, pyrogallol, inhibits the growth of HeLa cells via cell cycle arrest and apoptosis.

    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

    authors: Kim SW,Han YW,Lee ST,Jeong HJ,Kim SH,Kim IH,Lee SO,Kim DG,Kim SH,Kim SZ,Park WH

    更新日期:2008-02-01 00:00:00