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

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...

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Published in:Scientific reports 2021-04, Vol.11 (1), p.8847-17, Article 8847
Main Authors: Lottini, Tiziano, Iorio, Jessica, Lastraioli, Elena, Carraresi, Laura, Duranti, Claudia, Sala, Cesare, Armenio, Miriam, Noci, Ivo, Pillozzi, Serena, Arcangeli, Annarosa
Format: Article
Language:English
Subjects:
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Cell cycle
Deregulation
DNA microarrays
Endometrial cancer
Endometrium
Females
Gene regulation
Genetic transformation
Humanities and Social Sciences
Immune system
Immunohistochemistry
Luteinizing hormone
multidisciplinary
Oviduct
Reproductive system
Science
Science (multidisciplinary)
Transgenic mice
Tumors
Uterus
Xenobiotics
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-87492-5