Pten loss causes hypertrophy and increased proliferation of astrocytes in vivo

Melissa M. Fraser, Xiaoyan Zhu, Chang Hyuk Kwon, Erik J. Uhlmann, David H. Gutmann, Suzanne J. Baker

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)7773-7779
Number of pages7
JournalCancer research
Volume64
Issue number21
DOIs
StatePublished - Nov 1 2004

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