| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Akira Akita University, School of Medicine, Professor, 医学部, 教授 (10311565)
HAMADA Kouichi Akita University, School of Medicine, Assistant, 医学部, 助手 (00343070)
INOUE Tae Akita University, School of Medicine, Assistant, 医学部, 助手 (10301061)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Signal transducer and activator of transcription 3 (Stat3) is a transcription factor that is constitutively activated in a variety of human malignancies, including prostate, lung, brain, breast, and squamous cell carcinomas. Inhibition of activated Stat3 leads to decreased proliferation and apoptosis of many cancerderived cell lines, while the introduction of a constitutively activated form of Stat3 into immortalized human breast epithelial cells and rodent fibroblasts results in cellular transformation. Collectively, these data suggest a role for Stat3 in oncogenesis.
Since loss of phosphatase and tensin homolog (PTEN) gene contribute to oncogenesis in Cowdendisease, we examined Stat3 as the downstream target of the PTEN signaling pathways which have been shown to play important roles in the control of cell proliferation, apoptosis, and oncogenesis. Consequently, we demonstrated that the skin of PTEN-Stat3 deficient mice was wrinkled due to hyperplasia and their hair coats were abnormally ruffled and shaggy. Futhermore, histological findings revealed hyperkeratosis, hypergranulosis, papillomatous, acanthosis, the high density of the hair follicles and advanced development of sebaceous glands. Since these findings suggested that the appearances of PTEN-Stat3 deficient mice were completely identical to those of PTEN deficient mice, we cconcluded that the hyperproliferation of epidermis by PTEN deficiency was not recovered by Stat3 deficiency and that apoptosis in the bulge region of hair follicles by Stat3-deficiency was completely recovered by PTEN-deficiency.
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