+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice

Conditional loss of uterine Pten unfailingly and rapidly induces endometrial cancer in mice

Cancer Research 68(14): 5619-5627

Etiology of endometrial cancer (EMC) is not fully understood. Animal models with rapidly and spontaneously developing EMC will help explore mechanisms of cancer initiation and progression. Pten(+/-) mice are currently being used as a model to study EMC. These females develop atypical endometrial hyperplasia of which approximately 20% progresses to EMC. In addition, tumors develop in other organs, complicating the use of this model to specifically study EMC. Here, we show that conditional deletion of endometrial Pten results in EMC in all female mice as early as age 1 month with myometrial invasion occurring by 3 months. In contrast, conditional deletion of endometrial p53 had no phenotype within this time frame. Whereas mice with endometrial Pten deletion had a life span of approximately 5 months, mice with combined deletion of endometrial Pten and p53 had a shorter life span with an exacerbated disease state. Such rapid development of EMC from homozygous loss of endometrial Pten suggests that this organ is very sensitive to this tumor suppressor gene for tumor development. All lesions at early stages exhibited elevated Cox-2 and phospho-Akt levels, hallmarks of solid tumors. More interestingly, levels of two microRNAs miR-199a(*) and miR-101a that posttranscriptionally inhibit Cox-2 expression were down-regulated in tumors in parallel with Cox-2 up-regulation. This mouse model in which the loxP-Cre system has been used to delete endometrial Pten and/or p53 allows us to study in detail the initiation and progression of EMC. These mouse models have the added advantage because they mimic several features of human EMC.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 052287787

Download citation: RISBibTeXText

PMID: 18632614

DOI: 10.1158/0008-5472.CAN-08-1274

Related references

The uterine epithelial loss of Pten is inefficient to induce endometrial cancer with intact stromal Pten. Plos Genetics 14(8): E1007630-E1007630, 2018

Uterine double-conditional inactivation of Smad2 and Smad3 in mice causes endometrial dysregulation, infertility, and uterine cancer. Proceedings of the National Academy of Sciences of the United States of America 2019, 2019

The Synergistic Effect of Conditional Pten Loss and Oncogenic K-ras Mutation on Endometrial Cancer Development Occurs via Decreased Progesterone Receptor Action. Journal of Oncology 2010: 139087-139087, 2009

Conditional abrogation of transforming growth factor-β receptor 1 in PTEN-inactivated endometrium promotes endometrial cancer progression in mice. Journal of Pathology 243(1): 89-99, 2017

Modeling glands with PTEN deficient cells and microscopic methods for assessing PTEN loss: endometrial cancer as a model. Methods 77-78: 31-40, 2016

Loss of expression of MLH1, MSH2, MSH6, and PTEN related to endometrial cancer in 68 patients with endometrial hyperplasia. International Journal of Gynecological Pathology 22(2): 141-148, 2003

Conditional PTEN-deficient mice as a prostate cancer chemoprevention model. Asian Pacific Journal of Cancer Prevention 16(5): 1827-1831, 2016

LncRNA-GAS5 induces PTEN expression through inhibiting miR-103 in endometrial cancer cells. Journal of Biomedical Science 22(): 100-100, 2016

Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer Research 70(15): 6225-6232, 2010

Consequences of the loss of p53, RB1, and PTEN: relationship to gefitinib resistance in endometrial cancer. Gynecologic Oncology 106(1): 94-104, 2007

Loss of PTEN, p27, and Over-Expression of Phosphorylated-AKT are Associated with Advanced Stage Endometrioid Endometrial Cancer. Gynecologic Oncology 107(2): 373-373, 2007

Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer. Endocrine-Related Cancer 10(2): 203-208, 2003

PTEN loss detection in prostate cancer: comparison of PTEN immunohistochemistry and PTEN FISH in a large retrospective prostatectomy cohort. Oncotarget 8(39): 65566-65576, 2017

Conditional loss of Nkx3.1 in adult mice induces prostatic intraepithelial neoplasia. Molecular and Cellular Biology 22(5): 1495-1503, 2002

Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation. Cancer Research 68(17): 6902-6907, 2008