NDLI: GATA6 is an astrocytoma tumor suppressor gene identified by gene trapping of mouse glioma model

Content Provider	PubMed Central
Author	Deepak, Kamnasaran Qian, Baoping Hawkins, Cynthia Stanford, William L. Guha, Abhijit
Copyright Year	2007
Abstract	Malignant astrocytomas are the most common and lethal adult primary brain tumor. Retroviral gene trapping of nontransformed neonatal astrocytes from a glial fibrillary acidic protein (GFAP):V12Ha-Ras murine astrocytoma model led to isolation of the transcription factor Gata6. Loss of Gata6 resulted in enhanced proliferation and transformation of astrocytes. Human malignant astrocytoma cell lines, explant xenografts, and operative specimens demonstrated loss of GATA6 expression. Loss-of-function GATA6 mutations with loss of heterozygosity of the GATA6 locus were found in human malignant astrocytoma specimens but not in lower-grade astrocytomas or normal adult astrocytes. Knockdown of Gata6 expression in V12Ha-Ras or p53−/− astrocytes, but not in parental murine or human astrocytes, led to acceleration of tumorgenesis. Knockin GATA6 expression in human malignant astrocytoma cells reduced their tumorgenic growth with decreased VEGF expression. Collectively, these data demonstrate that GATA6, isolated from a murine astrocytoma model, is a novel tumor suppressor gene that is a direct target of mutations during malignant progression of murine and human astrocytomas. This work also demonstrates the utility of random mutagenesis strategies, such as gene trapping, on murine cancer models toward discovery of novel genetic alterations in corresponding human cancers.
Related Links	http://dx.doi.org/10.1073/pnas.0611669104
Ending Page	8058
Page Count	6
Starting Page	8053
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	104
Language	English
Publisher	National Academy of Sciences
Publisher Date	2007-05-08
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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