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[Cancer Research 64, 7773-7779, November 1, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Pten Loss Causes Hypertrophy and Increased Proliferation of Astrocytes In vivo

Melissa M. Fraser1, Xiaoyan Zhu1, Chang-Hyuk Kwon1,2, Erik J. Uhlmann3, David H. Gutmann3 and Suzanne J. Baker1

1 Department of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, Tennessee; 2 Center for Developmental Biology, University of Texas Southwestern Medical Center of Dallas, Dallas, Texas; and 3 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri

Somatic mutations of PTEN are found in many types of cancers including glioblastoma, the most malignant astrocytic tumor. PTEN mutation occurs in 25 to 40% of glioblastomas but is rarely observed in low-grade glial neoplasms. To determine the role of Pten in astrocytes and glial tumor formation, we inactivated Pten by a Cre-loxP approach with a GFAP-cre transgenic mouse that induced Cre-mediated recombination in astrocytes. Pten conditional knockout mice showed a striking progressive enlargement of the entire brain. Increased nuclear and soma size was observed in both astrocytes and neurons, which contributed in part to the increase in brain size. Pten-deficient astrocytes showed accelerated proliferation in vitro and aberrant ongoing proliferation in adult brains in vivo. In contrast, neurons lacking Pten did not show alterations in proliferation. This study shows cell-type dependent effects of Pten loss in the adult brain, including increased astrocyte proliferation that may render astroglial cells susceptible to neoplastic transformation or malignant progression.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2004 by the American Association for Cancer Research.