| First Author | Joshi A | Year | 2012 |
| Journal | Am J Pathol | Volume | 180 |
| Issue | 6 | Pages | 2536-47 |
| PubMed ID | 22503752 | Mgi Jnum | J:184698 |
| Mgi Id | MGI:5426092 | Doi | 10.1016/j.ajpath.2012.03.006 |
| Citation | Joshi A, et al. (2012) Endometrial Tumorigenesis in Pten(+/-) Mice Is Independent of Coexistence of Estrogen and Estrogen Receptor alpha. Am J Pathol 180(6):2536-47 |
| abstractText | Numerous studies support the role for mutations in the phosphatase and tensin homologue (PTEN) tumor suppressor gene and unopposed estrogen stimulation in the pathogenesis of uterine endometrioid carcinoma. However, the relation between PTEN signaling and estrogen/estrogen receptor in endometrial tumorigenesis remains unresolved. We used genetically engineered mice as a model to address this relation. Mice with a single deleted Pten allele (Pten(+/-)) spontaneously develop complex atypical hyperplasia and approximately 20% develop endometrial cancer. To determine the effect of removing endogenous estrogen, we performed oophorectomies on Pten(+/-) mice. Although there was a reduction in the number and severity of hyperplastic lesions, the endometrial phenotype persisted, suggesting that Pten mutation, independent of estrogen, can initiate the development of complex atypical hyperplasia. To recapitulate the situation in women with unopposed estrogen, we implanted 17beta-estradiol pellets in adult female Pten heterozygous mice, resulting in increased carcinoma incidence. Because studies have shown that estrogen largely acts on the endometrium via estrogen receptor ERalpha, we generated Pten(+/-)ERalpha(-/-) mice. Strikingly, 88.9% ofPten(+/-)ERalpha(-/-) mice developed endometrial hyperplasia/carcinoma. Furthermore, Pten(+/-)ERalpha(-/-) mice showed a higher incidence of in situ and invasive carcinoma, suggesting that endometrial tumorigenesis can progress in the absence of ERalpha. Thus, the relation between Pten alterations and estrogen signaling in the development of endometrial carcinoma is complex; the results presented herein have important implications for the treatment of endometrial hyperplasia and carcinoma in women. |
