title: Portrait of PTEN: messages from mutant mice.
abstract: PTEN is a tumor suppressor gene mutated in many human sporadic cancers and in hereditary cancer syndromes such as Cowden disease. The major substrate of PTEN is phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), a second messenger molecule produced following PI3K activation induced by a variety of stimuli. PI(3,4,5)P3 activates the serine-threonine kinase Akt, which is involved in antiapoptosis, proliferation and oncogenesis. In mice, heterozygosity for a null mutation of Pten (Pten(+/-)mice) frequently leads to the development of a variety of cancers and autoimmune disease. Homozygosity for the null mutation (Pten(-/-) mice) results in early embryonic lethality, precluding the functional analysis of Pten in adult tissues and organs. To investigate the physiological functions of Pten in viable mice, we and other groups have used the Cre-loxP system to generate various tissue-specific Pten mutations. The present review will summarize results obtained from the study of conditional mutant mice lacking Pten in specific tissues, and discuss the possible biological and molecular explanations for why Pten deficiency leads to tumorigenesis.
authors.affiliation: Division of Embryonic and Genetic Engineering, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. suzuki@bioreg.kyushu-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Tak Wah
authors.initials: TW
authors.lastname: Mak
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015603:Keratinocytes / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D013601:T-Lymphocytes / Q000378:metabolism; D019459:Urothelium / Q000378:metabolism
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse