Keratinocyte-Specific Pten Deficiency Results in Epidermal Hyperplasia, Accelerated Hair Follicle Morphogenesis and Tumor Formation1
[CANCER RESEARCH 63, 674–681, February 1, 2003] Keratinocyte-specific Pten Deficiency Results in Epidermal Hyperplasia, Accelerated Hair Follicle Morphogenesis and Tumor Formation1 Akira Suzuki, Satoshi Itami,2 Minako Ohishi,2 Koichi Hamada, Tae Inoue, Nobuyasu Komazawa, Haruki Senoo, Takehiko Sasaki, Junji Takeda, Motomu Manabe, Tak Wah Mak,3, 4 and Toru Nakano3, 5 Departments of Biochemistry [A. S., K. H.], Dermatology [T. I., M. M.], and Anatomy [H. S.], Akita University School of Medicine, Akita 010-8543, Japan; Department of Molecular Cell Biology, Research Institute for Microbial Disease [M. O., T. N.], Department of Dermatology [S. I.], and Department of Social and Environmental Medicine [N. K., J. T.], Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science, Tokyo 113-8613, Japan [T. S.]; and Advanced Medical Discovery Institute, University of Toronto, Toronto, Ontario, M5G 2C1 Canada [T. W. M.] ABSTRACT The epidermis of the skin is a keratinized and stratified squamous epithelium composed mainly of keratinocytes, cells whose prolifera- PTEN is a tumor suppressor gene mutated in many human cancers. We tion and differentiation must be tightly regulated and coordinated used the Cre-loxP system to generate a keratinocyte-specific null mutation (13–15). Keratinocytes first attach to the basal membrane of the of Pten in mice (k5Ptenflox/flox mice). k5Ptenflox/flox mice exhibit wrinkled skin because of epidermal hyperplasia and hyperkeratosis and ruffled, epidermis as undifferentiated precursor cells. These precursors mi- shaggy, and curly hair. Histological examination revealed that skin mor- grate toward the surface of the epidermis and subsequently form its phogenesis is accelerated in k5Ptenflox/flox mice.
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