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Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice

Yi Li; Katrina Podsypanina; Xiufan Liu; Allison Crane; Lee Tan; Ramon Parsons; Harold Varmus

Title:
Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice
Author(s):
Li, Yi
Podsypanina, Katrina
Liu, Xiufan
Crane, Allison
Tan, Lee
Parsons, Ramon
Varmus, Harold
Date:
Type:
Articles
Department(s):
Institute for Cancer Genetics
Volume:
2
Persistent URL:
Book/Journal Title:
BMC Molecular Biology
Abstract:
Background: Germline mutations in the tumor suppressor PTEN predispose human beings to breast cancer, and genetic and epigenetic alterations of PTEN are also detected in sporadic human breast cancer. Germline Pten mutations in mice lead to the development of a variety of tumors, but mammary carcinomas are infrequently found, especially in mice under the age of six months. Results: To better understand the role of PTEN in breast tumor development, we have crossed Pten heterozygous mice to MMTV-Wnt-1 transgenic mice that routinely develop ductal carcinomas in the mammary gland. Female Wnt-1 transgenics heterozygous for Pten developed mammary tumors earlier than Wnt-1 transgenics that were wild type for Pten. In most tumors arising in Pten heterozygotes, the Pten wild-type allele was lost, suggesting that cells lacking Pten function have a growth advantage over cells retaining a wild type allele. Tumors with LOH contained high levels of activated AKT/PKB, a downstream target of the PTEN/PI3K pathway. Conclusions: An animal model has been developed in which the absence of Pten collaborates with Wnt-1 to induce ductal carcinoma in the mammary gland. This animal model may be useful for testing therapies specific for tumors deregulated in the PTEN/PI3K/AKT pathway.
Subject(s):
Antioncogenes
Breast--Cancer
Breast--Cancer--Genetic aspects
Breast--Tumors
Breast--Cancer--Etiology
Carcinogenesis
Medicine
Oncology
Publisher DOI:
https://doi.org/10.1186/1471-2199-2-2
Item views
62
Metadata:
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Suggested Citation:
Yi Li, Katrina Podsypanina, Xiufan Liu, Allison Crane, Lee Tan, Ramon Parsons, Harold Varmus, , Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice, Columbia University Academic Commons, .

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