The EP1 subtype of prostaglandin E2 receptor: Role in keratinocyte differentiation and expression in non-melanoma skin cancer

Raymond Konger, S. D. Billings, N. C. Prall, T. M. Katona, S. C. DaSilva, C. R J Kennedy, Sunil Badve, Susan Perkins, P. T. LaCelle

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation.

Original languageEnglish
Pages (from-to)279-290
Number of pages12
JournalProstaglandins Leukotrienes and Essential Fatty Acids
Volume81
Issue number4
DOIs
StatePublished - Oct 2009

Fingerprint

Receptors, Prostaglandin E, EP1 Subtype
Skin Neoplasms
Keratinocytes
Skin
Epidermis
Prostaglandin E Receptors
Staining and Labeling
Membranes
Transglutaminases
Second Messenger Systems
Keratins
Up-Regulation
Cell Count
Cells
Calcium
Carcinoma
Polymerase Chain Reaction
Proteins

Keywords

  • Calcium mobilization
  • EP1 subtype of prostaglandin E2 receptor
  • Keratinocyte differentiation
  • Non-melanoma skin cancer

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Medicine(all)

Cite this

The EP1 subtype of prostaglandin E2 receptor : Role in keratinocyte differentiation and expression in non-melanoma skin cancer. / Konger, Raymond; Billings, S. D.; Prall, N. C.; Katona, T. M.; DaSilva, S. C.; Kennedy, C. R J; Badve, Sunil; Perkins, Susan; LaCelle, P. T.

In: Prostaglandins Leukotrienes and Essential Fatty Acids, Vol. 81, No. 4, 10.2009, p. 279-290.

Research output: Contribution to journalArticle

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