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端粒酶逆转录酶(TERT)表达、端粒酶活性以及基质金属蛋白酶(MMP)-1/-2/-9在与2型乳头瘤病毒感染相关的猫口腔鳞状细胞癌细胞系中的表达

Telomerase Reverse Transcriptase (TERT) Expression, Telomerase Activity, and Expression of Matrix Metalloproteinases (MMP)-1/-2/-9 in Feline Oral Squamous Cell Carcinoma Cell Lines Associated With Papillomavirus Type-2 Infection.

作者信息

Altamura Gennaro, Martano Manuela, Licenziato Luca, Maiolino Paola, Borzacchiello Giuseppe

机构信息

Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.

出版信息

Front Vet Sci. 2020 Mar 27;7:148. doi: 10.3389/fvets.2020.00148. eCollection 2020.

Abstract

Telomerase activity contributes to cell immortalization by avoiding telomere shortening at each cell division; indeed, its catalytic subunit telomerase reverse transcriptase (TERT) is overexpressed in many tumors, including human oral squamous cell carcinoma (hOSCC). In these tumors, matrix metalloproteinases (MMPs), a group of zinc-dependent endopeptidases involved in cell migration, contribute to invasive potential of cancer cells. A proportion of hOSCC is associated with infection by high-risk human papillomavirus (HR-HPVs), whose E6 oncogene enhances TERT and MMPs expression, thus promoting cancer progression. Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor with highly invasive phenotype; however, studies on telomerase activity, TERT, and MMPs expression are scarce. In this study, we demonstrate telomerase activity, expression of TERT, and its transcriptional activator cMyc along with expression of MMP-1, -2, and -9 in FOSCC-derived cell lines SCCF2 and SCCF3, suggesting a contribution by these pathways in cell immortalization and invasion in these tumors. Recent studies suggest that a sub-group of FOSCC as well as SCCF2 and SCCF3 are associated with PV type-2 (FcaPV-2) infection. However, in this work, FcaPV-2 E6 gene knock-down caused no shift in either TERT, cMyc, or MMPs levels, suggesting that, unlike its human counterpart, the viral oncogene plays no role in their regulation.

摘要

端粒酶活性通过避免每次细胞分裂时端粒缩短来促进细胞永生化;实际上,其催化亚基端粒酶逆转录酶(TERT)在包括人类口腔鳞状细胞癌(hOSCC)在内的许多肿瘤中均过表达。在这些肿瘤中,基质金属蛋白酶(MMPs)是一组参与细胞迁移的锌依赖性内肽酶,有助于癌细胞的侵袭潜能。一部分hOSCC与高危人乳头瘤病毒(HR-HPVs)感染有关,其E6癌基因可增强TERT和MMPs的表达,从而促进癌症进展。猫口腔鳞状细胞癌(FOSCC)是一种具有高度侵袭性表型的恶性肿瘤;然而,关于端粒酶活性、TERT和MMPs表达的研究却很少。在本研究中,我们证明了FOSCC来源的细胞系SCCF2和SCCF3中端粒酶活性、TERT及其转录激活因子cMyc的表达,以及MMP-1、-2和-9的表达,表明这些途径在这些肿瘤的细胞永生化和侵袭中发挥了作用。最近的研究表明,FOSCC以及SCCF2和SCCF3的一个亚组与2型乳头瘤病毒(FcaPV-2)感染有关。然而,在这项研究中,FcaPV-2 E6基因敲低并未导致TERT、cMyc或MMPs水平发生变化,这表明,与其人类对应物不同,病毒癌基因在它们的调控中不起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/981e/7118734/5d8145448d47/fvets-07-00148-g0001.jpg

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