Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus

Henderson, Ying C.; Breau, Randall L.; Liu, Ta Jën; Clayman, Gary L.

doi:10.1002/1097-0347(200007)22:4<347::aid-hed6>3.0.co;2-j

Cited by 46 publications

(32 citation statements)

References 32 publications

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“…Overexpression of p53, E2F, p16, p21, and p15 individually has been shown to induce premature growth arrest accompanied by inhibition of telomerase activity in head and neck squamous cell carcinoma and human glioma cell lines (73,102,115). Recent studies provide evidence that p53 inhibits telomerase activity through the transcriptional repression of hTERT (115,132,260).…”

Section: Transcriptional Regulation Of Htert Genementioning

confidence: 99%

“…Repression of telomerase activity by pRB was observed upon reestablishment of expression of pRB in pRB Ϫ p53 Ϫ tumor cells and was associated with cellular growth arrest (261). Repression of telomerase activity was also observed by overexpressing pRB in a human squamous cell carcinoma cell line (43,180) and overexpressing E2F1 in head and neck squamous cell carcinoma cell lines (102). However, these studies do not address the mechanisms by which pRB and E2F1 repress telomerase activity.…”

Section: Transcriptional Regulation Of Htert Genementioning

confidence: 99%

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Human Telomerase and Its Regulation

Cong

Wright

2002

Microbiol Mol Biol Rev

761

668

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The telomere is a special functional complex at the end of linear eukaryotic chromosomes, consisting of tandem repeat DNA sequences and associated proteins. It is essential for maintaining the integrity and stability of linear eukaryotic genomes. Telomere length regulation and maintenance contribute to normal human cellular aging and human diseases. The synthesis of telomeres is mainly achieved by the cellular reverse transcriptase telomerase, an RNA-dependent DNA polymerase that adds telomeric DNA to telomeres. Expression of telomerase is usually required for cell immortalization and long-term tumor growth. In humans, telomerase activity is tightly regulated during development and oncogenesis. The modulation of telomerase activity may therefore have important implications in antiaging and anticancer therapy. This review describes the currently known components of the telomerase complex and attempts to provide an update on the molecular mechanisms of human telomerase regulation

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Section: Transcriptional Regulation Of Htert Genementioning

confidence: 99%

Section: Transcriptional Regulation Of Htert Genementioning

confidence: 99%

Human Telomerase and Its Regulation

Cong

Wright

2002

Microbiol Mol Biol Rev

761

668

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“…9 MYC protein is a critical factor that activates telomerase through hTERT transcription in neoplasms including prostate cancer. 26 In contrast, p21 overexpression suppresses telomerase activity and hTERT mRNA expression in breast cancer cells 10 and head and neck tumors, 11 although the binding region for p21 has not yet been identified in the hTERT promoter. c-MYC or p21 may be a candidate modulator for the effects of HDAC inhibitors on hTERT mRNA expression.…”

Section: Effects Of Hdac Inhibitors On Androgen-independent Pc-3 Cellsmentioning

confidence: 99%

“…10,11 HDAC inhibitors, such as trichostatin A (TSA) and sodium butyrate (NaB), have been reported to decrease c-myc mRNA expression and increase p21 mRNA. 2 In addition, NaB and its analogues were previously reported to inhibit telomerase activity in leukemia cells 12 and nasopharyngeal cancer cells, 13 although there was no evaluation of hTERT mRNA.…”

mentioning

confidence: 99%

Histone deacetylase inhibitors suppress telomerase reverse transcriptase mrna expression in prostate cancer cells

Suenaga

Soda

Oka

et al. 2001

Intl Journal of Cancer

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Telomerase activity is involved in cellular immortality. We have recently demonstrated that telomerase activity is closely associated with cell proliferation in prostate cancers. Telomerase is composed primarily of the catalytic subunit (hTERT) and the RNA template (hTERC), and hTERT expression is regulated by several factors such as c-MYC and p21Waf1 . Histone deacetylase (HDAC) inhibitors are known to modulate transcription and exhibit antiproliferative effects on cancer cells. The present study was designed to evaluate the effects of HDAC inhibitors on hTERT mRNA expression in prostate cancer cells. LNCaP and PC-3 cells were treated with HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB); mRNA expression and telomerase activity were evaluated by RT-PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA expression was suppressed at 1 and 3 hr after treatment with 1 M TSA and 4 mM NaB, respectively, followed by inhibition of telomerase activity. The inhibition of hTERT mRNA expression preceded suppression of cell proliferation. In PC-3 cells, TSA and NaB also inhibited cell proliferation, hTERT mRNA expression and telomerase activity. In both cell lines, TSA and NaB had no effect on hTERC expression, or on expression of c-myc and p21Waf1 mRNA. These effects of TSA and NaB were unlikely to be consequences of cell cycle arrest, apoptosis, or cell differentiation. Thus, HDAC inhibitors down-regulated telomerase activity via suppression of hTERT mRNA expression. Our study identified a novel mechanism for the antiproliferative effects of HDAC inhibitors on prostate cancer cells.

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“…This leads to progression into the S phase (31). Studies have indicated that telomerase activity is correlated with high expression of cyclin D and low expression of p16INK4 (32)(33)(34). In the present study, inhibition of hTERT expression significantly altered the cell cycle profile of H1299 cells; the proportion of cells in G1 was increased (to 73.9%), while the percentage of cells in S and G2 phases was decreased.…”

Section: Discussionmentioning

confidence: 99%

Effect of plasmid-mediated RNA interference targeting telomerase reverse transcriptase on lung cancer cells

Deng

2011

Oncol Rep

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Abstract. In the present study, a plasmid-mediated siRNA interference vector targeting the hTERT gene was constructed and stably transfected into H1299 lung cancer cells. Using realtime quantitative fluorescent PCR technology, Western blotting and flow cytometry-based cell cycle profiling, the silencing effect of this vector and its inhibitory effect on proliferation in lung cancer cells were explored. Based upon the results of our previous study, a pair of siRNA sequences was selected, and a DNA template primer was designed and synthesized. After cloning of the template primer into the promoter of the pGenesil-1.1 expression vector, the constructed interference vector was validated using enzyme digestion and gene sequencing. The recombinant interference vector and empty vector were separately transfected into H1299 lung cancer cells with cationic liposomes, and stable monoclonally transfected cells were obtained after selection with G418. After stable transfection, hTERT mRNA and protein expression levels were detected using real-time RT-PCR technology and Western blotting. Using the MTT method and a colony formation assay, the growth and proliferation of the stably transfected lung cancer cells were determined. Changes in the cell cycle profile of the stably transfected lung cancer cells were detected using flow cytometry. An interference vector targeting the hTERT gene (pGenesil.1-hTERT) was successfully constructed. Enzyme digestion and gene sequencing confirmed that the sequence insertion met the criteria of the design. After transfection of H1299 cells with pGenesil

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Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus

Cited by 46 publications

References 32 publications

Human Telomerase and Its Regulation

Human Telomerase and Its Regulation

Histone deacetylase inhibitors suppress telomerase reverse transcriptase mrna expression in prostate cancer cells

Effect of plasmid-mediated RNA interference targeting telomerase reverse transcriptase on lung cancer cells

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