title: Pten deficiency in melanocytes results in resistance to hair graying and susceptibility to carcinogen-induced melanomagenesis.
abstract: Phosphate and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene inactivated in numerous sporadic cancers, including melanomas. To analyze Pten functions in melanocytes, we used the Cre-loxP system to delete Pten specifically in murine pigment-producing cells and generated DctCrePten(flox/flox) mice. Half of DctCrePten(flox/flox) mice died shortly after birth with enlargements of the cerebral cortex and hippocampus. Melanocytes were increased in the dermis of perinatal DctCrePten(flox/flox) mice. When the mutants were subjected to repeated depilations, melanocyte stem cells in the bulge of the hair follicle resisted exhaustion and the mice were protected against hair graying. Although spontaneous melanomas did not form in DctCrePten(flox/flox) mice, large nevi and melanomas developed after carcinogen exposure. DctCrePten(flox/flox) melanocytes were increased in size and exhibited heightened activation of Akt and extracellular signal-regulated kinases, increased expression of Bcl-2, and decreased expression of p27(Kip1). Our results show that Pten is important for the maintenance of melanocyte stem cells and the suppression of melanomagenesis.
authors.affiliation: Department of Dermatology, Akita University School of Medicine, Akita, Japan.
authors.forename: Tae
authors.initials: T
authors.lastname: Inoue-Narita
authors.forename: Koichi
authors.initials: K
authors.lastname: Hamada
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hatakeyama
authors.forename: Sachiko
authors.initials: S
authors.lastname: Fujita
authors.forename: Kohichi
authors.initials: K
authors.lastname: Kawahara
authors.forename: Masato
authors.initials: M
authors.lastname: Sasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Eguchi
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Tetsunori
authors.initials: T
authors.lastname: Kimura
authors.forename: Masatake
authors.initials: M
authors.lastname: Osawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
authors.forename: Tak Wah
authors.initials: TW
authors.lastname: Mak
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Motomu
authors.initials: M
authors.lastname: Manabe
authors.forename: Akira
authors.initials: A
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006200:Hair Color / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry; D008544:Melanocytes / Q000166:cytology* / Q000378:metabolism; D008545:Melanoma / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology
chemical_list: D002273:Carcinogens; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse