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

   


Authors: Li, Y.; Podsypanina, K.; Liu, X.; Crane, A.; Tan, L. K.; Parsons, R.; Varmus, H. E.
Article Title: Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice
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.
Keywords: protein kinase b; controlled study; gene mutation; nonhuman; protein function; animal cell; allele; animal tissue; cell growth; animal experiment; animal model; wild type; phosphatidylinositol 3 kinase; transgenic mouse; animalia; mus musculus; heterozygosity; breast carcinoma; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; protein induction; gene control; heterozygosity loss; breast carcinogenesis; mouse mammary tumor virus; wnt1 protein; male; female; article
Journal Title: BMC Molecular Biology
Volume: 2
ISSN: 1471-2199
Publisher: Biomed Central Ltd  
Date Published: 2001-01-23
Start Page: 2
Language: English
DOI: 10.1186/1471-2199-2-2
PROVIDER: scopus
PMCID: PMC29091
PUBMED: 11178110
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-2542451142&partnerID=40&md5=0172b8a3f007554a950097a64bb63ced
Notes: Export Date: 21 May 2015 -- Source: Scopus
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MSK Authors
  1. Yi Li
    8 Li
  2. Lee K Tan
    147 Tan
  3. Katrina Podsypanina
    15 Podsypanina
  4. Harold Varmus
    96 Varmus
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