Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer

Background: Since the most well-known function of thyroid hormone receptors (TRs) relies on their ability to act as ligand-activated transcription factors, their subcellular localization has been recognized to be relevant for their biological meaning. The current study aimed to determine the prevale...

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Main Authors: Sabine Heublein, Udo Jeschke, Cornelia Sattler, Christina Kuhn, Anna Hester, Bastian Czogalla, Fabian Trillsch, Sven Mahner, Doris Mayr, Elisa Schmoeckel, Nina Ditsch
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/5/2698
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author Sabine Heublein
Udo Jeschke
Cornelia Sattler
Christina Kuhn
Anna Hester
Bastian Czogalla
Fabian Trillsch
Sven Mahner
Doris Mayr
Elisa Schmoeckel
Nina Ditsch
author_facet Sabine Heublein
Udo Jeschke
Cornelia Sattler
Christina Kuhn
Anna Hester
Bastian Czogalla
Fabian Trillsch
Sven Mahner
Doris Mayr
Elisa Schmoeckel
Nina Ditsch
author_sort Sabine Heublein
collection DOAJ
description Background: Since the most well-known function of thyroid hormone receptors (TRs) relies on their ability to act as ligand-activated transcription factors, their subcellular localization has been recognized to be relevant for their biological meaning. The current study aimed to determine the prevalence and subcellular distribution of TR beta and TR beta-1 in ovarian cancer (OC). Methods: Tissue was collected from 153 patients that had undergone surgery due to OC at the Department of Obstetrics and Gynaecology of the Ludwig-Maximilians-University Munich. Immunohistochemistry detecting TR beta and TR beta-1 was performed. Staining signals were quantified and tested for association with clinico-pathological parameters including overall survival (OS). Results: The subcellular distribution of TR beta and TR beta-1 differed among histologic subtypes, grade and FIGO stage. TR beta positivity was strongly linked to shortened overall survival (<i>p</i> < 0.001). Strikingly, this shortened OS was mainly attributed to those cases showing complete (<i>p</i> = 0.005) or incomplete shift of TR beta to the cytoplasm (<i>p</i> < 0.001). Significance was lost in multivariate testing. Conclusions: Cytoplasmatic localization of TR beta was associated with reduced OS, at least in univariate analysis. Since TRs have long been supposed to mainly function via the regulation of gene transcription in the nucleus, cytoplasmatic shifting might be interpreted as a regulator of their activity.
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spelling doaj.art-84dc7de1d0ca48c0b525fe231ce9bac82023-11-23T23:08:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01235269810.3390/ijms23052698Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian CancerSabine Heublein0Udo Jeschke1Cornelia Sattler2Christina Kuhn3Anna Hester4Bastian Czogalla5Fabian Trillsch6Sven Mahner7Doris Mayr8Elisa Schmoeckel9Nina Ditsch10Department of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyDepartment of Pathology, LMU Munich, 80337 Munich, GermanyDepartment of Pathology, LMU Munich, 80337 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital LMU Munich, 81377 Munich, GermanyBackground: Since the most well-known function of thyroid hormone receptors (TRs) relies on their ability to act as ligand-activated transcription factors, their subcellular localization has been recognized to be relevant for their biological meaning. The current study aimed to determine the prevalence and subcellular distribution of TR beta and TR beta-1 in ovarian cancer (OC). Methods: Tissue was collected from 153 patients that had undergone surgery due to OC at the Department of Obstetrics and Gynaecology of the Ludwig-Maximilians-University Munich. Immunohistochemistry detecting TR beta and TR beta-1 was performed. Staining signals were quantified and tested for association with clinico-pathological parameters including overall survival (OS). Results: The subcellular distribution of TR beta and TR beta-1 differed among histologic subtypes, grade and FIGO stage. TR beta positivity was strongly linked to shortened overall survival (<i>p</i> < 0.001). Strikingly, this shortened OS was mainly attributed to those cases showing complete (<i>p</i> = 0.005) or incomplete shift of TR beta to the cytoplasm (<i>p</i> < 0.001). Significance was lost in multivariate testing. Conclusions: Cytoplasmatic localization of TR beta was associated with reduced OS, at least in univariate analysis. Since TRs have long been supposed to mainly function via the regulation of gene transcription in the nucleus, cytoplasmatic shifting might be interpreted as a regulator of their activity.https://www.mdpi.com/1422-0067/23/5/2698ovarian cancerthyroid hormone receptor betaprognosis
spellingShingle Sabine Heublein
Udo Jeschke
Cornelia Sattler
Christina Kuhn
Anna Hester
Bastian Czogalla
Fabian Trillsch
Sven Mahner
Doris Mayr
Elisa Schmoeckel
Nina Ditsch
Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
International Journal of Molecular Sciences
ovarian cancer
thyroid hormone receptor beta
prognosis
title Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
title_full Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
title_fullStr Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
title_full_unstemmed Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
title_short Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer
title_sort subcellular distribution of thyroid hormone receptor beta in ovarian cancer
topic ovarian cancer
thyroid hormone receptor beta
prognosis
url https://www.mdpi.com/1422-0067/23/5/2698
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