Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation Journal Article

  

Authors:	Xiao, A.; Wu, H.; Pandolfi, P. P.; Louis, D. N.; Van Dyke, T.
Article Title:	Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation
Abstract:	We have inactivated pRb, p107, and p130 in astrocytes by transgenic expression of T121 (a truncated SV40 T antigen) under the GFAP promoter. Founder mice died perinatally with extensive expansion of neural precursor and anaplastic astrocyte populations. In astrocytes, aberrant proliferation and extensive apoptosis were induced. Using a conditional allele of T121, early lethality was circumvented, and adult mice developed high-grade astrocytoma, in which regions of decreased apoptosis expressed activated Akt. Indeed, astrocytoma development was accelerated in a PTEN +/-, but not p53+/-, background. These studies establish a highly penetrant preclinical model for astrocytoma based on events observed in the human disease and further provide insight into the role of PTEN mutation in astrocytoma progression. Copyright © 2002 Cell Press.
Keywords:	signal transduction; protein kinase b; controlled study; protein expression; oncoprotein; promoter region; genetics; mutation; proto-oncogene proteins; cancer growth; nonhuman; cancer grading; cell proliferation; mouse; animal; metabolism; animals; mice; animal tissue; cell division; cancer susceptibility; genetic predisposition to disease; apoptosis; phosphatase; astrocyte; enzyme activation; pathology; protein serine threonine kinase; heterozygote; protein p53; carcinogenesis; transgenic mouse; mice, transgenic; brain; protein-serine-threonine kinases; tumor suppressor proteins; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; proto-oncogene proteins c-akt; pten phosphohydrolase; organ specificity; tumor suppressor protein p53; antibody specificity; aging; gene inactivation; tumor suppressor protein; malignant transformation; retinoblastoma protein; genetic predisposition; astrocytoma; phosphoric monoester hydrolases; nerve potential; astrocytes; transgenics; congenital malformation; astrocytosis; priority journal; article; induced mutation
Journal Title:	Cancer Cell
Volume:	1
Issue:	2
ISSN:	1535-6108
Publisher:	Cell Press
Date Published:	2002-03-01
Start Page:	157
End Page:	168
Language:	English
DOI:	10.1016/s1535-6108(02)00029-6
PUBMED:	12086874
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0036490954&partnerID=40&md5=c3347b720e0b7d627e5658ac0dbeddae
Notes:	Export Date: 14 November 2014 -- Source: Scopus

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