Epidermal Ras blockade demonstrates spatially localized Ras promotion of proliferation and inhibition of differentiation
- 27 February 2002
- journal article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 21 (10), 1527-1538
- https://doi.org/10.1038/sj.onc.1205287
Abstract
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.This publication has 51 references indexed in Scilit:
- Expression of Human Cystatin A by Keratinocytes Is Positively Regulated via the Ras/MEKK1/MKK7/JNK Signal Transduction Pathway but Negatively Regulated via the Ras/Raf-1/MEK1/ERK PathwayOnline Journal of Public Health Informatics, 2001
- Induction of β3-Integrin Gene Expression by Sustained Activation of the Ras-Regulated Raf–MEK–Extracellular Signal-Regulated Kinase Signaling PathwayMolecular and Cellular Biology, 2001
- Targeted Genomic Disruption of H-ras and N-ras, Individually or in Combination, Reveals the Dispensability of Both Loci for Mouse Growth and DevelopmentMolecular and Cellular Biology, 2001
- Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesisOncogene, 2000
- Reversible Activation of c-Myc in Skin: Induction of a Complex Neoplastic Phenotype by a Single Oncogenic LesionMolecular Cell, 1999
- Epidermal stem cells: markers, patterning and the control of stem cell fatePhilosophical Transactions B, 1998
- Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4aCell, 1997
- Transglutaminase 1 Delivery to Lamellar Ichthyosis KeratinocytesHuman Gene Therapy, 1996
- Induction of epidermal hyperplasia, hyperkeratosis, and papillomas in transgenic mice by a targeted v-Ha-ras oncogeneMolecular Carcinogenesis, 1993
- An activated Harvey ras oncogene produces benign tumours on mouse epidermal tissueNature, 1986