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Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer

The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 gene...

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Autores principales: Dratwa, Marta, Wysoczanska, Barbara, Brankiewicz, Wioletta, Stachowicz-Suhs, Martyna, Wietrzyk, Joanna, Matkowski, Rafał, Ekiert, Marcin, Szelachowska, Jolanta, Maciejczyk, Adam, Szajewski, Mariusz, Baginski, Maciej, Bogunia-Kubik, Katarzyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102200/
https://www.ncbi.nlm.nih.gov/pubmed/35563554
http://dx.doi.org/10.3390/ijms23095164
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author Dratwa, Marta
Wysoczanska, Barbara
Brankiewicz, Wioletta
Stachowicz-Suhs, Martyna
Wietrzyk, Joanna
Matkowski, Rafał
Ekiert, Marcin
Szelachowska, Jolanta
Maciejczyk, Adam
Szajewski, Mariusz
Baginski, Maciej
Bogunia-Kubik, Katarzyna
author_facet Dratwa, Marta
Wysoczanska, Barbara
Brankiewicz, Wioletta
Stachowicz-Suhs, Martyna
Wietrzyk, Joanna
Matkowski, Rafał
Ekiert, Marcin
Szelachowska, Jolanta
Maciejczyk, Adam
Szajewski, Mariusz
Baginski, Maciej
Bogunia-Kubik, Katarzyna
author_sort Dratwa, Marta
collection PubMed
description The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness.
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spelling pubmed-91022002022-05-14 Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer Dratwa, Marta Wysoczanska, Barbara Brankiewicz, Wioletta Stachowicz-Suhs, Martyna Wietrzyk, Joanna Matkowski, Rafał Ekiert, Marcin Szelachowska, Jolanta Maciejczyk, Adam Szajewski, Mariusz Baginski, Maciej Bogunia-Kubik, Katarzyna Int J Mol Sci Article The molecular mechanisms of telomerase reverse transcriptase (TERT) upregulation in breast cancer (BC) are complex. We compared genetic variability within TERT and telomere length with the clinical data of patients with BC. Additionally, we assessed the expression of the TERT, MYC, TP53 and SP1 genes in BC patients and in BC organoids (3D cell cultures obtained from breast cancer tissues). We observed the same correlation in the blood of BC patients and in BC organoids between the expression of TERT and TP53. Only in BC patients was a correlation found between the expression of the TERT and MYC genes and between TP53 and MYC. We found associations between TERT genotypes (rs2735940 and rs10069690) and TP53 expression and telomere length. BC patients with the TT genotype rs2735940 have a shorter telomere length, but patients with A allele rs10069690 have a longer telomere length. BC patients with a short allele VNTR-MNS16A showed higher expression of the SP1 and had a longer telomere. Our results bring new insight into the regulation of TERT, MYC, TP53 and SP1 gene expression related to TERT genetic variability and telomere length. Our study also showed for the first time a similar relationship in the expression of the above genes in BC patients and in BC organoids. These findings suggest that TERT genetic variability, expression and telomere length might be useful biomarkers for BC, but their prognostic value may vary depending on the clinical parameters of BC patients and tumor aggressiveness. MDPI 2022-05-05 /pmc/articles/PMC9102200/ /pubmed/35563554 http://dx.doi.org/10.3390/ijms23095164 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dratwa, Marta
Wysoczanska, Barbara
Brankiewicz, Wioletta
Stachowicz-Suhs, Martyna
Wietrzyk, Joanna
Matkowski, Rafał
Ekiert, Marcin
Szelachowska, Jolanta
Maciejczyk, Adam
Szajewski, Mariusz
Baginski, Maciej
Bogunia-Kubik, Katarzyna
Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title_full Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title_fullStr Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title_full_unstemmed Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title_short Relationship between Telomere Length, TERT Genetic Variability and TERT, TP53, SP1, MYC Gene Co-Expression in the Clinicopathological Profile of Breast Cancer
title_sort relationship between telomere length, tert genetic variability and tert, tp53, sp1, myc gene co-expression in the clinicopathological profile of breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102200/
https://www.ncbi.nlm.nih.gov/pubmed/35563554
http://dx.doi.org/10.3390/ijms23095164
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