In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 16, No. 14_Supplement ( 2010-07-15), p. B23-B23
Abstract:
Adenomyosis is a common gynecological disorder defined by the presence of endometrial glands and stroma within the myometrium. Despite its frequent occurrence, the precise etiology of adenomyosis is still unknown, although it has often been associated with endometrioid adenocarcinoma. β-catenin abnormalities are common in endometrioid type endometrial carcinomas. The expression of the dominant stabilized β-catenin in the murine uterus (PRcre/+ Ctnnb1f(ex3)/+) resulted in endometrial glandular hyperplasia. In addition to the glandular hyperplasia phenotype, uteri of PRcre/+ Ctnnb1f(ex3)/+ mice exhibited an abnormal myometrial structure and proceed to develop adenomyosis. Ablation of Mig-6 in the murine uterus (PRcre/+ Mig-6f/f) leads to the development of endometrial hyperplasia and estrogen-induced endometrial cancer. Concomitant stabilization of β -catenin and ablation of Mig-6 dramatically accelerated the development of adenomyosis and glandular hyperplasia compared to stablizing β-catenin alone. The adenomyosis phenotype of ovariectomized Pffre/+ Ctnnb1f & lt;ex3)/+ and PRcre/+ Ctnnb1f(ex3)/+Mig-6f/f mice manifests in the presence of E2 and P4, but not, however, in the absence of ovarian hormones. Importantly, increased nuclear β-catenin expression and decreased MIG-6 expression was observed in women with adenomyosis, providing compelling support for and implicating an important role of β-catenin and MIG-6 in the etiology of adenomyosis in both humans and mice. We have demonstrated that abnormal activation of β-catenin induces adenomyosis formation and ablation of Mig-6 accelerates the progress of adenomyosis formation in the murine uterus. These mouse models are useful and allow us to investigate in detail the initiation and progression of adenomyosis because they mimic several features of human adenomyosis. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B23.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1078-0432.TCMUSA10-B23
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
