Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors

An In Vivo Xenograft Model of Keratoacanthoma

Steven D. Billings, Michael D. Southall, Tao Li, Paul W. Cook, LeeAnn Baldridge, William B. Moores, Dan Spandau, John Foley, Jeffrey Travers

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2451-2458
Number of pages8
JournalAmerican Journal of Pathology
Volume163
Issue number6
StatePublished - Dec 2003

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Keratoacanthoma
Heterografts
Neoplasms
Squamous Cell Carcinoma
Basal Cell Carcinoma
Keratinocytes
Amphiregulin
Fibroblast Growth Factor 7
SCID Mice
Serum-Free Culture Media
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Billings, S. D., Southall, M. D., Li, T., Cook, P. W., Baldridge, L., Moores, W. B., ... Travers, J. (2003). Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors: An In Vivo Xenograft Model of Keratoacanthoma. American Journal of Pathology, 163(6), 2451-2458.

Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors : An In Vivo Xenograft Model of Keratoacanthoma. / Billings, Steven D.; Southall, Michael D.; Li, Tao; Cook, Paul W.; Baldridge, LeeAnn; Moores, William B.; Spandau, Dan; Foley, John; Travers, Jeffrey.

In: American Journal of Pathology, Vol. 163, No. 6, 12.2003, p. 2451-2458.

Research output: Contribution to journalArticle

Billings SD, Southall MD, Li T, Cook PW, Baldridge L, Moores WB et al. Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors: An In Vivo Xenograft Model of Keratoacanthoma. American Journal of Pathology. 2003 Dec;163(6):2451-2458.
Billings, Steven D. ; Southall, Michael D. ; Li, Tao ; Cook, Paul W. ; Baldridge, LeeAnn ; Moores, William B. ; Spandau, Dan ; Foley, John ; Travers, Jeffrey. / Amphiregulin Overexpression Results in Rapidly Growing Keratinocytic Tumors : An In Vivo Xenograft Model of Keratoacanthoma. In: American Journal of Pathology. 2003 ; Vol. 163, No. 6. pp. 2451-2458.
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