OBJECTIVE: Endometrial cancer (EMC) is the most common gynecological malignancy. The etiology and the cell types that are conducive to EMC are not completely understood, provoking further studies. Our objective was to determine whether deletion of Pten specifically in the uterine stroma and myometrium induces cancer or manifests different phenotypes. METHODS: Pten(Amhr2(d/d)) mice with conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, were generated by mating floxed Pten mice and anti-Mullerian hormone type 2 receptor (Amhr2)-Cre mice. The phenotypes were compared between Pten(f/f) and Pten(Amhr2(d/d)) uteri. RESULTS: We show that conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, fails to generate EMC even at the age of 5 months. Surprisingly Pten deletion by Amhr2-Cre transformed a large number of myometrial cells into adipocytes with lipid accumulation, possibly a result of increased levels of SREBP1 and PPARγ which regulate adipose differentiation. CONCLUSIONS: These results provide evidence that deletion of Pten specifically in the stroma and myometrium does not result in EMC in female mice examined up to 5 months of age but alters the myocytes to adipocytes and mimics histologic similarities with lipoleiomyomas in humans, raising the possibility of using this mouse model to further explore the cause of the disease.
OBJECTIVE:Endometrial cancer (EMC) is the most common gynecological malignancy. The etiology and the cell types that are conducive to EMC are not completely understood, provoking further studies. Our objective was to determine whether deletion of Pten specifically in the uterine stroma and myometrium induces cancer or manifests different phenotypes. METHODS:Pten(Amhr2(d/d)) mice with conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, were generated by mating floxed Ptenmice and anti-Mullerian hormone type 2 receptor (Amhr2)-Cre mice. The phenotypes were compared between Pten(f/f) and Pten(Amhr2(d/d)) uteri. RESULTS: We show that conditional deletion of Pten in the mouse uterine stroma and myometrium, but not in the epithelium, fails to generate EMC even at the age of 5 months. Surprisingly Pten deletion by Amhr2-Cre transformed a large number of myometrial cells into adipocytes with lipid accumulation, possibly a result of increased levels of SREBP1 and PPARγ which regulate adipose differentiation. CONCLUSIONS: These results provide evidence that deletion of Pten specifically in the stroma and myometrium does not result in EMC in female mice examined up to 5 months of age but alters the myocytes to adipocytes and mimics histologic similarities with lipoleiomyomas in humans, raising the possibility of using this mouse model to further explore the cause of the disease.
Authors: Michael A Crackower; Gavin Y Oudit; Ivona Kozieradzki; Renu Sarao; Hui Sun; Takehiko Sasaki; Emilio Hirsch; Akira Suzuki; Tetsuo Shioi; Junko Irie-Sasaki; Rajan Sah; Hai-Ying M Cheng; Vitalyi O Rybin; Giuseppe Lembo; Luigi Fratta; Antonio J Oliveira-dos-Santos; Jeffery L Benovic; C Ronald Kahn; Seigo Izumo; Susan F Steinberg; Matthias P Wymann; Peter H Backx; Josef M Penninger Journal: Cell Date: 2002-09-20 Impact factor: 41.582
Authors: Sanaz Memarzadeh; Yang Zong; Deanna M Janzen; Andrew S Goldstein; Donghui Cheng; Takeshi Kurita; Amanda M Schafenacker; Jiaoti Huang; Owen N Witte Journal: Proc Natl Acad Sci U S A Date: 2010-09-20 Impact factor: 11.205
Authors: Soazik P Jamin; Nelson A Arango; Yuji Mishina; Mark C Hanks; Richard R Behringer Journal: Mol Cell Endocrinol Date: 2003-12-15 Impact factor: 4.102
Authors: Yevgeniya J Ioffe; Katherine B Chiappinelli; David G Mutch; Israel Zighelboim; Paul J Goodfellow Journal: Gynecol Oncol Date: 2011-10-15 Impact factor: 5.482
Authors: Mingxin Shi; Allison E Whorton; Nikola Sekulovski; Marilène Paquet; James A MacLean; Yurong Song; Terry Van Dyke; Kanako Hayashi Journal: Biol Reprod Date: 2020-04-24 Impact factor: 4.285