Cell-specific conditional deletion of Pten in the uterus results in differential phenotypes
T Daikoku, L Jackson, V Besnard, J Whitsett… - Gynecologic …, 2011 - Elsevier
T Daikoku, L Jackson, V Besnard, J Whitsett, LH Ellenson, SK Dey
Gynecologic oncology, 2011•ElsevierOBJECTIVE: 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: PtenAmhr2 (d/d) mice with conditional deletion of Pten in the
mouse uterine stroma and myometrium, but not in the epithelium, were generated by mating …
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: PtenAmhr2 (d/d) mice with conditional deletion of Pten in the
mouse uterine stroma and myometrium, but not in the epithelium, were generated by mating …
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
PtenAmhr2(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 Ptenf/f and PtenAmhr2(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 5months. 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 5months 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.
Elsevier