ob/ob obese mice promote tumorigenesis of endometrial cancer associated with Pten deficiency

in Endocrine-Related Cancer
Authors:
Keun Cheon Kim Department of Obstetrics, Gynecology & Women’s Health, University of Missouri, Columbia, Missouri, USA

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Amanda Hull Department of Obstetrics, Gynecology & Women’s Health, University of Missouri, Columbia, Missouri, USA

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Eric Johannsen Department of Pathology Medical Science Building (MSB), University of Missouri, Columbia, Missouri, USA

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Mark I Hunter Department of Obstetrics, Gynecology & Women’s Health, University of Missouri, Columbia, Missouri, USA

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Tae Hoon Kim Department of Obstetrics, Gynecology & Women’s Health, University of Missouri, Columbia, Missouri, USA

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Jae-Wook Jeong Department of Obstetrics, Gynecology & Women’s Health, University of Missouri, Columbia, Missouri, USA

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https://orcid.org/0000-0002-5368-6478

Correspondence should be addressed to J-W Jeong: Jeongjw@missouri.edu
DOI:
https://doi.org/10.1530/ERC-24-0228
Volume/Issue:
Volume 32: Issue 5
Article Type:
Research Article
Article ID:
e240228
Online Publication Date:
27 Mar 2025
Copyright:
© the author(s) 2025
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Obesity refers to the condition of being overweight due to abnormal fat accumulation and is highly associated with the development of various cancers. Endometrial cancer is the most diagnosed gynecologic cancer. Obesity is a strong risk factor for endometrial cancer. However, the etiological and pathophysiological effects of obesity on endometrial cancer have not been fully understood. To determine the effect of obesity on tumorigenesis in endometrial cancer, we examined the effect of obesity on tumorigenesis using genetically engineered mouse models, including an obesity model (ob/ob), an endometrial cancer model (Pgrcre/+Ptenf/f ; Ptend/d ), and an endometrial cancer with obesity model (Pgrcre/+Ptenf/fob/ob; Ptend/dob/ob). Histopathological analysis was performed on the uteri of the three groups during tumorigenesis. From 1.5 months of age, the body and uterine weight of Ptend/dob/ob mice were significantly higher than those of the Ptend/d mice. Ptend/dob/ob mice had higher tumor grade with myometrial invasion at 1.5 and 2 months than Ptend/d mice. The levels of phospho-histone H3, a proliferation marker and phospho-STAT3 were significantly increased in the endometrial cancer of Ptend/dob/ob mice compared to Ptend/d mice. Our results suggest that obesity accelerates the progression of endometrial cancer associated with Pten mutation.

Supplementary Materials

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Full Text Views 72 72 52
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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2025
Article ID:
e240228
Received Date:
29 Aug 2024
Rev-recd:
13 Feb 2025
Accepted Date:
19 Mar 2025
Print Publication Date:
01 May 2025
Online Publication Date:
27 Mar 2025
Keywords:
endometrial cancer; obesity; PTEN; leptin; mouse model

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