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Role of tesmin expression in non-small cell lung cancer
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells duri...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709552/ https://www.ncbi.nlm.nih.gov/pubmed/33281959 http://dx.doi.org/10.3892/ol.2020.12309 |
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author | Grzegrzolka, Jedrzej Olbromski, Mateusz Gomulkiewicz, Agnieszka Piotrowska, Aleksandra Glatzel-Plucinska, Natalia Ratajczak, Katarzyna Sputa-Grzegrzolka, Patrycja Rzechonek, Adam Werynska, Bozena Podhorska-Okolow, Marzena Dziegiel, Piotr |
author_facet | Grzegrzolka, Jedrzej Olbromski, Mateusz Gomulkiewicz, Agnieszka Piotrowska, Aleksandra Glatzel-Plucinska, Natalia Ratajczak, Katarzyna Sputa-Grzegrzolka, Patrycja Rzechonek, Adam Werynska, Bozena Podhorska-Okolow, Marzena Dziegiel, Piotr |
author_sort | Grzegrzolka, Jedrzej |
collection | PubMed |
description | Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells during spermatogenesis. Increased tesmin expression in NSCLC has been described previously. Minichromosome maintenance proteins (MCMs) serve a critical role in replication and cell cycle progression, i.e. in NSCLC. The aim of the present study was to evaluate the localization and intensity of tesmin, MCM5 and MCM7 protein expression in NSCLC and their association with the clinicopathological data of patients. Archival paraffin blocks of 243 cases of NSCLC and 104 non-cancerous tissue samples from the surgical margin (control) were obtained from patients treated at the Clinic of Thoracic Surgery of Wroclaw Medical University (Wroclaw, Poland) between 2010 and 2016, and were used for tissue microarrays and immunohistochemical (IHC) experiments. Laser capture microdissection was used for the isolation of cancer cells from 36 frozen samples of NSCLC and 8 control samples, and subsequently, MTL5, MCM5 and MCM7 mRNA expression was detected separately by reverse transcription-quantitative PCR. Positive cytoplasmic and nuclear tesmin, as well as nuclear MCM5 and MCM7 IHC expression were observed in 95.1, 83.67, 95.51 and 100% of the NSCLC cases, respectively. MTL5, MCM5 and MCM7 mRNA expression was observed in 91.66% of the cancer cases for all genes. The statistical analysis revealed increased tesmin IHC expression in cancer cells compared with the control. A positive correlation was observed between the IHC expression of nuclear tesmin and MCM5 proteins (r=0.33; P<0.0001) and nuclear tesmin and MCM7 proteins (r=0.315; P<0.0001). In addition, a positive correlation between the mRNA expression levels of MTL5 and MCM5 (r=0.421; P<0.05), MTL5 and MCM7 (r=0.557; P<0.01) was demonstrated. The survival analysis revealed that the presence of IHC cytoplasmic tesmin expression was a positive prognostic marker in NSCLC (P=0.0524). Furthermore, in vitro experiments performed on the NCI-H1703 cell line revealed that silencing of MTL5 mRNA and tesmin caused the downregulation of the expression levels of MCM5 and MCM7 and decreased the number of cells in the G2 phase. A positive association among tesmin, MCM5 and MCM7 could indicate a possible role of tesmin in the proliferation of NSCLC cancer cells. |
format | Online Article Text |
id | pubmed-7709552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-77095522020-12-03 Role of tesmin expression in non-small cell lung cancer Grzegrzolka, Jedrzej Olbromski, Mateusz Gomulkiewicz, Agnieszka Piotrowska, Aleksandra Glatzel-Plucinska, Natalia Ratajczak, Katarzyna Sputa-Grzegrzolka, Patrycja Rzechonek, Adam Werynska, Bozena Podhorska-Okolow, Marzena Dziegiel, Piotr Oncol Lett Articles Non-small cell lung cancer (NSCLC) is the most commonly diagnosed cancer and the most frequent cause of cancer-associated mortality worldwide. Tesmin (MTL5) is a 60 kDa protein which has cysteine rich motifs, characteristic of metallothioneins. Tesmin expression was first observed in germ cells during spermatogenesis. Increased tesmin expression in NSCLC has been described previously. Minichromosome maintenance proteins (MCMs) serve a critical role in replication and cell cycle progression, i.e. in NSCLC. The aim of the present study was to evaluate the localization and intensity of tesmin, MCM5 and MCM7 protein expression in NSCLC and their association with the clinicopathological data of patients. Archival paraffin blocks of 243 cases of NSCLC and 104 non-cancerous tissue samples from the surgical margin (control) were obtained from patients treated at the Clinic of Thoracic Surgery of Wroclaw Medical University (Wroclaw, Poland) between 2010 and 2016, and were used for tissue microarrays and immunohistochemical (IHC) experiments. Laser capture microdissection was used for the isolation of cancer cells from 36 frozen samples of NSCLC and 8 control samples, and subsequently, MTL5, MCM5 and MCM7 mRNA expression was detected separately by reverse transcription-quantitative PCR. Positive cytoplasmic and nuclear tesmin, as well as nuclear MCM5 and MCM7 IHC expression were observed in 95.1, 83.67, 95.51 and 100% of the NSCLC cases, respectively. MTL5, MCM5 and MCM7 mRNA expression was observed in 91.66% of the cancer cases for all genes. The statistical analysis revealed increased tesmin IHC expression in cancer cells compared with the control. A positive correlation was observed between the IHC expression of nuclear tesmin and MCM5 proteins (r=0.33; P<0.0001) and nuclear tesmin and MCM7 proteins (r=0.315; P<0.0001). In addition, a positive correlation between the mRNA expression levels of MTL5 and MCM5 (r=0.421; P<0.05), MTL5 and MCM7 (r=0.557; P<0.01) was demonstrated. The survival analysis revealed that the presence of IHC cytoplasmic tesmin expression was a positive prognostic marker in NSCLC (P=0.0524). Furthermore, in vitro experiments performed on the NCI-H1703 cell line revealed that silencing of MTL5 mRNA and tesmin caused the downregulation of the expression levels of MCM5 and MCM7 and decreased the number of cells in the G2 phase. A positive association among tesmin, MCM5 and MCM7 could indicate a possible role of tesmin in the proliferation of NSCLC cancer cells. D.A. Spandidos 2021-01 2020-11-17 /pmc/articles/PMC7709552/ /pubmed/33281959 http://dx.doi.org/10.3892/ol.2020.12309 Text en Copyright: © Grzegrzolka et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Grzegrzolka, Jedrzej Olbromski, Mateusz Gomulkiewicz, Agnieszka Piotrowska, Aleksandra Glatzel-Plucinska, Natalia Ratajczak, Katarzyna Sputa-Grzegrzolka, Patrycja Rzechonek, Adam Werynska, Bozena Podhorska-Okolow, Marzena Dziegiel, Piotr Role of tesmin expression in non-small cell lung cancer |
title | Role of tesmin expression in non-small cell lung cancer |
title_full | Role of tesmin expression in non-small cell lung cancer |
title_fullStr | Role of tesmin expression in non-small cell lung cancer |
title_full_unstemmed | Role of tesmin expression in non-small cell lung cancer |
title_short | Role of tesmin expression in non-small cell lung cancer |
title_sort | role of tesmin expression in non-small cell lung cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709552/ https://www.ncbi.nlm.nih.gov/pubmed/33281959 http://dx.doi.org/10.3892/ol.2020.12309 |
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