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Effect of PRL‐3 phosphatase knockout in cancer and angiogenesis
Author(s) -
Zimmerman Mark W,
Isenberg Jeffery S,
Homanics Gregg E,
Lazo John S
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1013.3
Subject(s) - protein tyrosine phosphatase , knockout mouse , biology , phosphatase , cancer research , angiogenesis , cancer , colorectal cancer , gene product , phenotype , in vivo , metastasis , endocrinology , medicine , gene expression , gene , signal transduction , microbiology and biotechnology , phosphorylation , genetics
Phosphatase of regenerating liver–3 (PRL‐3 or Ptp4a3) is a small, prenylated, protein tyrosine phosphatase that is highly conserved throughout mammalian species. PRL‐3 is considered an attractive therapeutic target for the treatment of metastatic cancer due to high expression levels frequently observed in malignant tumors, distant metastases, and the tumor endothelium. While the mechanistic properties of PRL‐3 are not well understood, the gene has been associated with the progression of multiple human cancer types and increased expression typically correlates with increased tumor invasiveness. Interestingly, our data suggests that increases in PRL‐3 expression can also occur early in a carcinogen‐derived mouse model of colorectal cancer, potentially contributing to primary tumor development. In order to shed light on its function in normal and malignant cells, we have created a novel gene‐targeted mouse model to knockout the PRL‐3 gene product. Importantly, mice that do not express functional PRL‐3 are viable, fertile, and overtly normal. PRL‐3 knockout mice exhibit less angiogenic responses and vascular cell invasion compared to wildtype control mice. These experiments indicate that PRL‐3 likely has unique in vivo functions and may be an effective target for the treatment of malignant disease.