PTEN is a dual protein ; lipid phosphatase and hereditary heterozygous mutation of
PTEN is associated in humans with Cowden disease, a rare autosomal dominant familial syndrome with a high risk of developing benign and malignant tumors in many organ systems. To investigate the role of
PTEN in skin development and oncogenesis, we used the
Cre-loxP system to generate a keratinocyte-specific null mutation of
Pten in mice (
k5Ptenflox/flox mice).
k5Ptenflox/flox mice exhibit wrinkled skin as the result of epidermal hyperplasia and hyperkeratosis and ruffled, shaggy, and curly hair. Histological examination revealed that skin morphogenesis is accelerated in
k5Ptenflox/flox mice. All
k5Ptenflox/flox mice develop spontaneous tumors within 8.5 months of birth.
PTEN is thus an essential regulator of normal homeostasis and oncogenesis in the skin.
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