Article

Prognostic value of human telomerase reverse transcriptase gene expression in oral carcinogenesis

Department of Surgical Sciences, University of Foggia, Foggia, Italy.
International Journal of Oncology (Impact Factor: 3.03). 07/2007; 30(6):1349-57. DOI: 10.3892/ijo.30.6.1349
Source: PubMed

ABSTRACT

Human telomerase reverse transcriptase (hTERT) gene expression in resected specimens of oral squamous cell carcinoma (OSCC) and their surrounding tissue, either apparently normal or clearly histologically dysplastic, was evaluated by both real-time RT-PCR and immunohisto-chemical protein analyses. The expression level of hTERT in oral dysplasia and in OSCC was markedly higher than in normal tissues. The correlation between hTERT expression in OSCC and clinico-pathological parameters or survival of OSCC patients was statistically analyzed. Our study demonstrates that there is no significant relationship between hTERT expression and classical clinico-pathological parameters. Interestingly, survival analysis showed both overexpressing cases and lower survival rate in the early stage of OSCC (p=0.03 for immunohistochemistry; p=0.04 for RT real-time PCR). The histological location of hTERT in these tumors has been discussed in the context of the cancer stem cell theory.

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    • "High levels of human telomerase reverse transcriptase (hTERT) mRNA expression and TA were restricted to proliferating tissues e.g. embryo, testis (Martin-Rivera et al., 1998; Greenberg et al., 1998; Hiyama and Hiyama, 2003; Park et al., 2004; Pannone et al., 2007; Herbert et al., 2007). In vivo studies using non-tumor tissues further revealed a good correlation between TA, cell proliferation and apoptosis (Inui et al., 2002; Oh et al., 2002; Lamy et al., 2013). "
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    ABSTRACT: Telomerase expression has long been linked to promotion of tumor growth and cell proliferation in mammals. Interestingly, telomerase activity (TA) has been detected in skeletal muscle for a variety of fish species. Despite this being a unique feature in fish, very few studies have investigated the potential role of TA in muscle. The present study was set to prove the concepts that muscle telomerase in fish is related to body growth, and more specifically, to muscle cell proliferation and apoptosis in vivo. Moreover, muscle TA can be influenced by biotic factors and modulated by environmental stress. Using three fish species, mangrove red snapper (Lutjanus argentimaculatus), orange-spotted grouper (Epinephelus coioides), and marine medaka (Oryzias melastigma), the present work reports for the first time that fish muscle TA was sensitive to the environmental stresses of starvation, foodborne exposure to benzo[a]pyrene, and hypoxia. In marine medaka, muscle TA was coupled with fish growth during early life stages. Upon sexual maturation, muscle TA was confounded by sex (female > male). Muscle TA was significantly correlated with telomerase reverse transcriptase (TERT) protein expression (Pearson correlation r = 0.892; p ≤ 0.05), which was coupled with proliferating cell nuclear antigen (PCNA) cell proliferation, but not associated with apoptosis (omBax/omBcl2 ratio) in muscle tissue. The results reported here have bridged the knowledge gap between the existence and function of telomerase in fish muscle. The underlying regulatory mechanisms of muscle TA in fish warrant further exploration for comparison with telomerase regulation in mammals.
    No preview · Article · Sep 2015 · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology
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    • "Kumar et al110 and Chen et al111 found that the expression of hTERT increased significantly from normal through OED to OSCC. At both the mRNA and protein levels, the expression of hTERT in OED and in OSCC was markedly higher than in normal tissues.109,112 Thus overexpression of immortalization marker may occur early in oral carcinogenesis and may be used as a diagnostic indicator in OED; however, its prognostic value remains unknown. "
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    ABSTRACT: Many attempts have been made to identify objective molecular biomarkers to diagnose and prognosticate oral epithelial dysplasia (OED) because histopathological interpretation is subjective and lacks sensitivity. The majority of these efforts describe changes in gene expression at protein level in OED as determined by immunohistochemistry (IHC). However, the literature on these putative markers of oral cancer progression is vast and varied. The main purpose of this article is to review current knowledge on biomarkers of protein expression for OED by IHC approaches. We further discuss these findings in terms of the proposed essential hallmarks of cancer cells to better understand their role in oral oncogenesis.
    Full-text · Article · Oct 2013
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    • "region, which was commonly present among the ODFs/OPMLs. This gene was reported to play a crucial role in telomere maintenance, chromosomal instability, DNA repair, negative regulation of apoptosis and was found to be amplified in several human cancers [39–42]. "
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    ABSTRACT: Oral fields of visually normal and non-dysplastic mucosa (ODFs) may represent the precursors of oral potentially malignant lesions (OPMLs). Aim of the study was to provide new evidence for the concept of the "field carcinogenesis" model by comparing the ODF and OPML genomic aberration profiles obtained by high resolution DNA flow cytometry (hr DNA-FCM) and array-Comparative Genomic Hybridization (a-CGH). A second aim was to investigate if specific CGH aberrations were associated with DNA aneuploidy. Nineteen patients with single OPMLs were recruited for the study. In parallel with obtaining samples of OPML tissue from 11 leukoplakias without dysplasia (nd-OPMLs) and 8 with dysplasia (d-OPMLs), we also obtained samples from distant ODFs. DNA aneuploid nuclei detected by hr DNA-FCM were physically separated, based on DNA content, from the DNA diploid components with a DNA-FCM-Sorter. These relatively pure subpopulations of epithelial nuclei were then submitted to DNA extraction and a-CGH for a genome-wide analysis of DNA copy number aberrations (CNAs). The frequencies of DNA aneuploidy (DI ≠ 1) among ODFs and OPMLs were respectively 5.3% and 32%. The DI aneuploid values of ODFs and nd-OPMLs were all near-diploid (DI ≠ 1 and DI ≤ 1.4), while for d-OPMLs were high-aneuploid (DI > 1.4) in 40% of the cases. CNA averages were 1.9 in ODFs and 6.5 in OPMLs. The gain of the chromosomal region 20q13.33-qter was observed in 37% of both ODFs and corresponding OPMLs. Additional common regions included 7p22.2-pter, 11p15.5-pter and 16p13.3-pter where gains were observed. Furthermore, gains of 20q13.31-q13.33 and of 5p13.33-pter and loss of 9p21.3 were detected at high frequency (respectively, at 62.5%, 50% and 50%) only in d-OPMLs. In particular, loss at 9p21.3, gain at 5p13.33-pter and gain of 20q13.31-q13.33 were associated with DNA aneuploidy (p = 0.00004; p = 0.0005; p = 0.01). ODFs and OPMLs showed common CNAs in specific chromosomal regions suggesting that they may represent early events of the natural history of oral carcinogenesis according to the field effect cancerization and may contribute to the ODF-OPML transition. In addition, loss at 9p21.3 and gains at 5p13.33-pter and 20q13.31-q13.33 may contribute to DNA aneuploidization.
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