Abstract
Lysophosphatidic acid (LPA) acts through high-affinity G protein-coupled receptors to mediate a plethora of physiological and pathological activities associated with tumorigenesis. LPA receptors and autotaxin (ATX/LysoPLD), the primary enzyme producing LPA, are aberrantly expressed in multiple cancer lineages. However, the role of ATX and LPA receptors in the initiation and progression of breast cancer has not been evaluated. We demonstrate that expression of ATX or each edg family LPA receptor in mammary epithelium of transgenic mice is sufficient to induce a high frequency of late-onset, estrogen receptor (ER)-positive, invasive, and metastatic mammary cancer. Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma / metabolism*
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Adenocarcinoma / secondary
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Animals
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Carcinoma, Adenosquamous / metabolism*
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Carcinoma, Adenosquamous / pathology
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Cloning, Molecular
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Female
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Humans
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Lung Neoplasms / metabolism
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Lung Neoplasms / secondary
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Lymphatic Metastasis
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Male
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Mammary Neoplasms, Experimental / metabolism*
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Mammary Neoplasms, Experimental / pathology
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Mice
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Mice, Transgenic
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism*
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Neoplasm Invasiveness
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Phosphodiesterase I / genetics
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Phosphodiesterase I / metabolism*
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Phosphoric Diester Hydrolases
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Pyrophosphatases / genetics
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Pyrophosphatases / metabolism*
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Receptors, Estrogen / metabolism
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / physiology*
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Signal Transduction / physiology
Substances
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Multienzyme Complexes
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Receptors, Estrogen
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Receptors, Lysophosphatidic Acid
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Phosphoric Diester Hydrolases
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Phosphodiesterase I
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alkylglycerophosphoethanolamine phosphodiesterase
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Pyrophosphatases