Physiological functions of Pten in mouse tissues.
PTEN is a tumor suppressor gene mutated in many human sporadic cancers and in hereditary cancer syndromes such as Cowden disease, Bannayan-Zonana syndrome and Lhermitte-Duclos disease. The major substrate of PTEN is PIP3, a second messenger molecule produced following PI3K activation induced by variety of stimuli. PIP3 activates the serine-threonine kinase PKB/Akt which is involved in anti-apoptosis, 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 various organs. To investigate the physiological functions of Pten in viable mice, various tissue-specific Pten mutations have been generated using the Cre-loxP system. This review will summarize the phenotypes of conditional mutant mice lacking Pten function in specific tissues, and discuss how these phenotypes relate to the physiological roles of Pten in various organ systems.
Kishimoto
Hiroyuki
H
Department of Biochemistry, Akita University School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan.
Hamada
Koichi
K
Saunders
Mary
M
Backman
Stephanie
S
Sasaki
Takehiko
T
Nakano
Toru
T
Mak
Tak Wah
TW
Suzuki
Akira
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000378:metabolism; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005804:Genes, Lethal / Q000235:genetics; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000172:deficiency* / Q000235:genetics
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human