Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors
| Autor: | Tao Li, Michael D. Southall, Lee Ann Baldridge, John Foley, Daniel F. Spandau, Paul W. Cook, Steven D. Billings, Jeffrey B. Travers, William B. Moores |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Pathology
medicine.medical_specialty Keratoacanthoma integumentary system Biology medicine.disease medicine.disease_cause Pathology and Forensic Medicine Transplantation chemistry.chemical_compound HaCaT medicine.anatomical_structure Amphiregulin chemistry Cell culture medicine Cancer research Keratinocyte growth factor skin and connective tissue diseases Carcinogenesis Keratinocyte |
| Zdroj: | The American Journal of Pathology. 163:2451-2458 |
| ISSN: | 0002-9440 |
| Popis: | Keratoacanthoma (KA) is a variant of cutaneous squamous cell carcinoma (SCC) known for rapid growth and potential for involution. Little is known about the basis for the rapid growth because of the dearth of model systems. We hypothesized that amphiregulin (AR), a keratinocyte autocrine growth factor, had a significant role. Using immunohistochemistry, we compared 21 KA, 6 conventional SCC, and 6 basal cell carcinomas (BCC) for AR expression. All KA were positive for AR, the majority with strong immunoreactivity. The SCC were positive (5 of 6), with generally weak staining; no BCC were positive. We developed laboratory model systems to study AR overexpression in keratinocytes and its role in the pathogenesis of KA. A retroviral transduction strategy was used to overexpress AR in the HaCaT keratinocyte-like cell line. The AR overexpressing cells (HaCaT-AR) displayed autonomous proliferation in serum-free media when compared with controls (HaCaT-NIE). To develop an in vivo model, xenografts of HaCaT-AR and HaCaT-NIE were grown on SCID mice. The HaCaT-NIE cells formed thin tumors resembling conventional SCC. The HaCaT-AR cells formed rapidly growing tumors with AR expression similar to KA. HaCaT-AR cells may represent a new system for the further evaluation of KA. |
| Databáze: | OpenAIRE |
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