%0 Journal Article
%T Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice
%A Yi Li
%A Katrina Podsypanina
%A Xiufan Liu
%A Allison Crane
%A Lee K Tan
%A Ramon Parsons
%A Harold E Varmus
%J BMC Molecular Biology
%D 2001
%I BioMed Central
%R 10.1186/1471-2199-2-2
%X 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.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.Cancer evolves from the accumulation of mutations and the deregulation of two classes of genes, oncogenes and tumor suppressor genes. The large majority of breast cancers arise in epithelia of the breast, and they are thought to evolve from hyperplasia with atypia to carcinoma in situ, invasive carcinoma, and, finally, metastatic disease. The molecular mechanisms leading to breast malignancies are unclear, but many genetic abnormalities and epigenetic factors have been implicated, including changes affecting known tumor suppressor genes (p53, BRCA1, BRCA2, PTEN/MMAC1/TEP1) and proto-oncogenes (neu/ErbB2/HER2, ErbB1/EGFR, PRAD-1/cyclin D1, Mdm2, and c-myc) [reviewed in ref. 1].The gene product of PTEN (phosphatase and tensin homolog deleted from chromosome 10) is a lipid phosphatase that reverses the activities of phosphatidylinositol 3-kinase (PI3K) by dephosphorylating the D3 position of its lipid products, phosphatidylinositol-3, 4 bis-phosphate (PtdIns(3,4)P2), phosphatidylinositol-3,5 bis-phosphate (PtdIns(3,5)P2), and 3,4,5-tri-phosphate (PtdIns(3,4,5)P3) [2, 3], the elevated levels of which are li
%U http://www.biomedcentral.com/1471-2199/2/2