Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements
Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in no...
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doaj-11f26454aa6647a889e1de236391c9252021-02-04T00:00:39ZengMDPI AGJournal of Clinical Medicine2077-03832021-02-011056056010.3390/jcm10040560Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive ElementsNatalia Rusetska0Paulina Kober1Sylwia Katarzyna Król2Joanna Boresowicz3Maria Maksymowicz4Jacek Kunicki5Wiesław Bonicki6Mateusz Bujko7Department of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Neurosurgery, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Molecular and Translational Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandPurpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary tumors. Methods: We investigated LINE-1 methylation levels in 80 tumors and normal pituitary glands with bisulfite-pyrosequencing. Expression of two LINE-1 open reading frames (<i>L1-ORF1</i> and <i>L1-ORF2</i>) was analyzed with qRT-<i>PCR</i> in tumor samples and mouse gonadotroph pituitary cells treated with DNA methyltransferase inhibitor. Immunohistochemical staining against L1-ORF1p was also performed in normal pituitary glands and tumors. Results: Hypomethylation of LINE-1 was observed in pituitary tumors. Tumors characterized by invasive growth revealed lower LINE-1 methylation level than noninvasive ones. LINE-1 methylation correlated with overall DNA methylation assessed with HM450K arrays and negatively correlated with <i>L1-ORF1</i> and <i>L1-ORF2</i> expression. Treatment of αT3-1 gonadotroph cells with 5-Azacytidine clearly increased the level of <i>L1-ORF1</i> and <i>L1-ORF2</i> mRNA; however, its effect on LβT2 cells was less pronounced. Immunoreactivity against L1-ORF1p was higher in tumors than normal tissue. No difference in L1-ORF1p expression was observed in invasive and noninvasive tumors. Conclusion: Hypomethylation of LINE-1 is related to invasive growth and influences transcriptional activity of transposable elements.https://www.mdpi.com/2077-0383/10/4/560DNA methylationLINE-1L1-ORF1ppituitary tumorgonadotropinomainvasive growth |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natalia Rusetska Paulina Kober Sylwia Katarzyna Król Joanna Boresowicz Maria Maksymowicz Jacek Kunicki Wiesław Bonicki Mateusz Bujko |
spellingShingle |
Natalia Rusetska Paulina Kober Sylwia Katarzyna Król Joanna Boresowicz Maria Maksymowicz Jacek Kunicki Wiesław Bonicki Mateusz Bujko Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements Journal of Clinical Medicine DNA methylation LINE-1 L1-ORF1p pituitary tumor gonadotropinoma invasive growth |
author_facet |
Natalia Rusetska Paulina Kober Sylwia Katarzyna Król Joanna Boresowicz Maria Maksymowicz Jacek Kunicki Wiesław Bonicki Mateusz Bujko |
author_sort |
Natalia Rusetska |
title |
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements |
title_short |
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements |
title_full |
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements |
title_fullStr |
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements |
title_full_unstemmed |
Invasive and Noninvasive Nonfunctioning Gonadotroph Pituitary Tumors Differ in DNA Methylation Level of LINE-1 Repetitive Elements |
title_sort |
invasive and noninvasive nonfunctioning gonadotroph pituitary tumors differ in dna methylation level of line-1 repetitive elements |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2021-02-01 |
description |
Purpose: Epigenetic dysregulation plays a role in pituitary tumor pathogenesis. Some differences in DNA methylation were observed between invasive and noninvasive nonfunctioning gonadotroph tumors. This study sought to determine the role of DNA methylation changes in repetitive LINE-1 elements in nonfunctioning gonadotroph pituitary tumors. Methods: We investigated LINE-1 methylation levels in 80 tumors and normal pituitary glands with bisulfite-pyrosequencing. Expression of two LINE-1 open reading frames (<i>L1-ORF1</i> and <i>L1-ORF2</i>) was analyzed with qRT-<i>PCR</i> in tumor samples and mouse gonadotroph pituitary cells treated with DNA methyltransferase inhibitor. Immunohistochemical staining against L1-ORF1p was also performed in normal pituitary glands and tumors. Results: Hypomethylation of LINE-1 was observed in pituitary tumors. Tumors characterized by invasive growth revealed lower LINE-1 methylation level than noninvasive ones. LINE-1 methylation correlated with overall DNA methylation assessed with HM450K arrays and negatively correlated with <i>L1-ORF1</i> and <i>L1-ORF2</i> expression. Treatment of αT3-1 gonadotroph cells with 5-Azacytidine clearly increased the level of <i>L1-ORF1</i> and <i>L1-ORF2</i> mRNA; however, its effect on LβT2 cells was less pronounced. Immunoreactivity against L1-ORF1p was higher in tumors than normal tissue. No difference in L1-ORF1p expression was observed in invasive and noninvasive tumors. Conclusion: Hypomethylation of LINE-1 is related to invasive growth and influences transcriptional activity of transposable elements. |
topic |
DNA methylation LINE-1 L1-ORF1p pituitary tumor gonadotropinoma invasive growth |
url |
https://www.mdpi.com/2077-0383/10/4/560 |
work_keys_str_mv |
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