Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses

Abstract The receptor for the luteinizing hormone (LH-R) is aberrantly over expressed in cancers of the reproductive system. To uncover whether LH-R over expression has a causative role in cancer, we generated a transgenic (TG) mouse which overexpresses the human LH-R (hLH-R) in the female reproduct...

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Autores principales:	Tiziano Lottini, Jessica Iorio, Elena Lastraioli, Laura Carraresi, Claudia Duranti, Cesare Sala, Miriam Armenio, Ivo Noci, Serena Pillozzi, Annarosa Arcangeli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9a6e45993e194c3c83cd4fdcbae104e0
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spelling	oai:doaj.org-article:9a6e45993e194c3c83cd4fdcbae104e02021-12-02T16:45:15ZTransgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses10.1038/s41598-021-87492-52045-2322https://doaj.org/article/9a6e45993e194c3c83cd4fdcbae104e02021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87492-5https://doaj.org/toc/2045-2322Abstract The receptor for the luteinizing hormone (LH-R) is aberrantly over expressed in cancers of the reproductive system. To uncover whether LH-R over expression has a causative role in cancer, we generated a transgenic (TG) mouse which overexpresses the human LH-R (hLH-R) in the female reproductive tract, under the control of the oviduct-specific glycoprotein (OGP) mouse promoter (mogp-1). The transgene was highly expressed in the uterus, ovary and liver, but only in the uterus morphological and molecular alterations (increased proliferation and trans-differentiation in the endometrial layer) were detected. A transcriptomic analysis on the uteri of young TG mice showed an up regulation of genes involved in cell cycle control and a down regulation of genes related to the immune system and the metabolism of xenobiotics. Aged TG females developed tumor masses in the uteri, which resembled an Endometrial Cancer (EC). Microarray and immunohistochemistry data indicated the deregulation of signaling pathways which are known to be altered in human ECs. The analysis of a cohort of 126 human ECs showed that LH-R overexpression is associated with early-stage tumors. Overall, our data led support to conclude that LH-R overexpression may directly contribute to trigger the neoplastic transformation of the endometrium.Tiziano LottiniJessica IorioElena LastraioliLaura CarraresiClaudia DurantiCesare SalaMiriam ArmenioIvo NociSerena PillozziAnnarosa ArcangeliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiziano Lottini Jessica Iorio Elena Lastraioli Laura Carraresi Claudia Duranti Cesare Sala Miriam Armenio Ivo Noci Serena Pillozzi Annarosa Arcangeli Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
description	Abstract The receptor for the luteinizing hormone (LH-R) is aberrantly over expressed in cancers of the reproductive system. To uncover whether LH-R over expression has a causative role in cancer, we generated a transgenic (TG) mouse which overexpresses the human LH-R (hLH-R) in the female reproductive tract, under the control of the oviduct-specific glycoprotein (OGP) mouse promoter (mogp-1). The transgene was highly expressed in the uterus, ovary and liver, but only in the uterus morphological and molecular alterations (increased proliferation and trans-differentiation in the endometrial layer) were detected. A transcriptomic analysis on the uteri of young TG mice showed an up regulation of genes involved in cell cycle control and a down regulation of genes related to the immune system and the metabolism of xenobiotics. Aged TG females developed tumor masses in the uteri, which resembled an Endometrial Cancer (EC). Microarray and immunohistochemistry data indicated the deregulation of signaling pathways which are known to be altered in human ECs. The analysis of a cohort of 126 human ECs showed that LH-R overexpression is associated with early-stage tumors. Overall, our data led support to conclude that LH-R overexpression may directly contribute to trigger the neoplastic transformation of the endometrium.
format	article
author	Tiziano Lottini Jessica Iorio Elena Lastraioli Laura Carraresi Claudia Duranti Cesare Sala Miriam Armenio Ivo Noci Serena Pillozzi Annarosa Arcangeli
author_facet	Tiziano Lottini Jessica Iorio Elena Lastraioli Laura Carraresi Claudia Duranti Cesare Sala Miriam Armenio Ivo Noci Serena Pillozzi Annarosa Arcangeli
author_sort	Tiziano Lottini
title	Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
title_short	Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
title_full	Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
title_fullStr	Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
title_full_unstemmed	Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses
title_sort	transgenic mice overexpressing the lh receptor in the female reproductive system spontaneously develop endometrial tumour masses
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9a6e45993e194c3c83cd4fdcbae104e0
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Transgenic mice overexpressing the LH receptor in the female reproductive system spontaneously develop endometrial tumour masses

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