Co-expression of p16INK4A and Laminin 5 by Keratinocytes: A Wound-Healing Response Coupling Hypermotility with Growth Arrest that Goes Awry During Epithelial Neoplastic Progression
| Autor: | Easwar Natarajan, Jonathan C.R. Jones, James G. Rheinwald, John D. Omobono |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Senescence
Keratinocytes Pathology medicine.medical_specialty senescence Stromal cell tumor suppressor Dermatology Biology law.invention Cell Line In vivo law Laminin Cell Movement Transforming Growth Factor beta epidermis medicine Humans Neoplasms Glandular and Epithelial Molecular Biology Cellular Senescence Cyclin-Dependent Kinase Inhibitor p16 Cell Proliferation Wound Healing Epidermis (botany) human cells General Medicine Cell Biology In vitro Cancer research biology.protein Carcinoma Squamous Cell Disease Progression Suppressor Tumor Suppressor Protein p53 Wound healing Biotechnology |
| Zdroj: | Journal of Investigative Dermatology Symposium Proceedings. 10(2):72-85 |
| ISSN: | 1087-0024 |
| DOI: | 10.1111/j.1087-0024.2005.200415.x |
| Popis: | The replicative lifespan of human keratinocytes in culture is restricted by a telomere-unrelated induction of p16INK4A (p16) and p14ARF. We have found that, in vivo, p16 is expressed by epidermal and oral keratinocytes at the migrating fronts of healing wounds and at the stromal interface of severely dysplastic and early invasive lesions and that such cells also invariably display increased expression of Laminin 5 (Lam5). In culture, p16 and Lam5 are coexpressed in keratinocytes at senescence, at the edges of wounds made in confluent cultures, and when cells are plated on dishes coated with the gamma2 precursor form of Lam5 (Lam5gamma2pre). Lam5/p16 coexpression in all three in vitro settings is associated with directional hypermotility and growth arrest. Hypermotility and growth arrest are uncoupled in p16- and p14ARF/p53-deficient keratinocytes and squamous cell carcinoma (SCC) cells; such cells become hypermotile is response to Lam5gamma2pre but do not growth arrest. Thus, the Lam5/p16 response is activated in normal wound healing, causing growth arrest of migratory keratinocytes that lead wound reepithelialization. This response also becomes activated at a critical stage of neoplastic progression, acting as a tumor suppressor mechanism. Rare premalignant cells that lose p16 remain motile and proliferative, thereby resulting in invasive growth as SCC. |
| Databáze: | OpenAIRE |
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