In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway

Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of...

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Autores principales:	Renata Pavlič, Marija Gjorgoska, Eva Hafner, Maša Sinreih, Kristina Gajser, Stefan Poschner, Walter Jäger, Tea Lanišnik Rižner
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	sulfatase pathway steroid sulfatase endometrial cancer estrone sulfate estrone sulfate transporters 17beta-hydroxysteroid dehydrogenase Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6336b51297f74a35b21700fe0aaeb502
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spelling	oai:doaj.org-article:6336b51297f74a35b21700fe0aaeb5022021-11-05T10:37:08ZIn the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway2296-889X10.3389/fmolb.2021.743403https://doaj.org/article/6336b51297f74a35b21700fe0aaeb5022021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.743403/fullhttps://doaj.org/toc/2296-889XEndometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly differentiated EC: RL95-2 and KLE cells, respectively. Results revealed high expression of estrone-sulfate (E1-S) transporters (SLCO1A2, SLCO1B3, SLCO1C1, SLCO3A1, SLC10A6, SLC22A9), and increased E1-S uptake in KLE vs RL95-2 cells. In RL95-2 cells, higher levels of sulfatase and better metabolism of E1-S to E1 were confirmed compared to KLE cells. In KLE cells, disturbed balance in expression of HSD17B genes led to enhanced activation of E1 to E2, compared to RL95-2 cells. Additionally, increased CYP1B1 expression and down-regulation of genes encoding phase II metabolic enzymes: COMT, NQO1, NQO2, and GSTP1 suggested decreased detoxification of carcinogenic metabolites in KLE cells. Results indicate that in model cell lines of moderately and poorly differentiated EC, estrogens can be formed via the sulfatase pathway.Renata PavličMarija GjorgoskaEva HafnerMaša SinreihKristina GajserStefan PoschnerWalter JägerTea Lanišnik RižnerFrontiers Media S.A.articlesulfatase pathwaysteroid sulfataseendometrial cancerestrone sulfateestrone sulfate transporters17beta-hydroxysteroid dehydrogenaseBiology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sulfatase pathway steroid sulfatase endometrial cancer estrone sulfate estrone sulfate transporters 17beta-hydroxysteroid dehydrogenase Biology (General) QH301-705.5
spellingShingle	sulfatase pathway steroid sulfatase endometrial cancer estrone sulfate estrone sulfate transporters 17beta-hydroxysteroid dehydrogenase Biology (General) QH301-705.5 Renata Pavlič Marija Gjorgoska Eva Hafner Maša Sinreih Kristina Gajser Stefan Poschner Walter Jäger Tea Lanišnik Rižner In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
description	Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly differentiated EC: RL95-2 and KLE cells, respectively. Results revealed high expression of estrone-sulfate (E1-S) transporters (SLCO1A2, SLCO1B3, SLCO1C1, SLCO3A1, SLC10A6, SLC22A9), and increased E1-S uptake in KLE vs RL95-2 cells. In RL95-2 cells, higher levels of sulfatase and better metabolism of E1-S to E1 were confirmed compared to KLE cells. In KLE cells, disturbed balance in expression of HSD17B genes led to enhanced activation of E1 to E2, compared to RL95-2 cells. Additionally, increased CYP1B1 expression and down-regulation of genes encoding phase II metabolic enzymes: COMT, NQO1, NQO2, and GSTP1 suggested decreased detoxification of carcinogenic metabolites in KLE cells. Results indicate that in model cell lines of moderately and poorly differentiated EC, estrogens can be formed via the sulfatase pathway.
format	article
author	Renata Pavlič Marija Gjorgoska Eva Hafner Maša Sinreih Kristina Gajser Stefan Poschner Walter Jäger Tea Lanišnik Rižner
author_facet	Renata Pavlič Marija Gjorgoska Eva Hafner Maša Sinreih Kristina Gajser Stefan Poschner Walter Jäger Tea Lanišnik Rižner
author_sort	Renata Pavlič
title	In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
title_short	In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
title_full	In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
title_fullStr	In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
title_full_unstemmed	In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway
title_sort	in the model cell lines of moderately and poorly differentiated endometrial carcinoma, estrogens can be formed via the sulfatase pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6336b51297f74a35b21700fe0aaeb502
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In the Model Cell Lines of Moderately and Poorly Differentiated Endometrial Carcinoma, Estrogens Can Be Formed via the Sulfatase Pathway

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