Epidermal Ras blockade demonstrates spatially localized Ras promotion of proliferation and inhibition of differentiation

• Published in: Oncogene Vol. 21; no. 10; pp. 1527 - 1538
• Main Authors: DAJEE, Maya, TARUTANI, Masahito, DENG, Helen, TI CAI, KHAVARI, Paul A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 28.02.2002; Nature Publishing Group
• Subjects: Adipocytes; Animals; Biological and medical sciences; Carcinogenesis; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Division; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cells, Cultured; Epidermis; Epidermis - cytology; Epidermis - metabolism; Fundamental and applied biological sciences. Psychology; Homeostasis; Humans; Immunohistochemistry; Integrins - immunology; Integrins - metabolism; Keratin; Keratinocytes - metabolism; Kinases; Mice; Mice, Transgenic; Microscopy, Fluorescence; Models, Biological; Molecular and cellular biology; Mutation; Proto-Oncogene Proteins c-raf - metabolism; Proto-Oncogene Proteins p21(ras) - antagonists & inhibitors; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - physiology; Raf protein; Regulation M; Signal Transduction; Transgenic animals; Palo Alto California; United States > US; California; Human; Cell proliferation; Signal transduction; C-Onc gene; Homeostasis; Skin; Cell differentiation; Epithelium
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1205287

While important in carcinogenesis, the role of Ras in normal self-renewing tissues such as epidermis is unclear. To address this, we altered Ras function in undifferentiated and differentiating epidermal layers. Ras blockade within undifferentiated basal epidermal cells leads to decreased integrin expression, diminished growth capacity and induction of differentiation. Ras blockade in post-mitotic suprabasal epidermis exerts no effect. In contrast, regulated Ras and Raf activation inhibits differentiation. These findings indicate that spatially restricted Ras/Raf signaling divides epidermis into an undifferentiated proliferative compartment and a differentiating post-mitotic compartment and suggest a new role for Ras in tissue homeostasis.