Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness

Sabine Brouxhon, Raymond L. Konger, Jo Anne VanBuskirk, Tzong Jen Sheu, Julie Ryan, Brandon Erdle, Anthony Almudevar, Richard M. Breyer, Glynis Scott, Alice P. Pentland

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE 2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP 2 -/- cells.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalJournal of Investigative Dermatology
Volume127
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Dinoprostone
Tumors
Carcinogenesis
Keratinocytes
Squamous Cell Carcinoma
Animals
Hairless Mouse
Neoplasms
Metalloproteases
Ultraviolet Rays
Growth
Carcinogens
Hypertrophy
Skin
Irradiation
Phenotype
Wounds and Injuries
Enzymes
Epithelial Cells

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. / Brouxhon, Sabine; Konger, Raymond L.; VanBuskirk, Jo Anne; Sheu, Tzong Jen; Ryan, Julie; Erdle, Brandon; Almudevar, Anthony; Breyer, Richard M.; Scott, Glynis; Pentland, Alice P.

In: Journal of Investigative Dermatology, Vol. 127, No. 2, 01.02.2007, p. 439-446.

Research output: Contribution to journalArticle

Brouxhon, S, Konger, RL, VanBuskirk, JA, Sheu, TJ, Ryan, J, Erdle, B, Almudevar, A, Breyer, RM, Scott, G & Pentland, AP 2007, 'Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness', Journal of Investigative Dermatology, vol. 127, no. 2, pp. 439-446. https://doi.org/10.1038/sj.jid.5700547
Brouxhon, Sabine ; Konger, Raymond L. ; VanBuskirk, Jo Anne ; Sheu, Tzong Jen ; Ryan, Julie ; Erdle, Brandon ; Almudevar, Anthony ; Breyer, Richard M. ; Scott, Glynis ; Pentland, Alice P. / Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness. In: Journal of Investigative Dermatology. 2007 ; Vol. 127, No. 2. pp. 439-446.
@article{bcd2b807b9584926b26dacd2750b54d8,
title = "Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness",
abstract = "Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE 2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50{\%} fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP 2 -/- cells.",
author = "Sabine Brouxhon and Konger, {Raymond L.} and VanBuskirk, {Jo Anne} and Sheu, {Tzong Jen} and Julie Ryan and Brandon Erdle and Anthony Almudevar and Breyer, {Richard M.} and Glynis Scott and Pentland, {Alice P.}",
year = "2007",
month = "2",
day = "1",
doi = "10.1038/sj.jid.5700547",
language = "English (US)",
volume = "127",
pages = "439--446",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Deletion of prostaglandin E2 EP2 receptor protects against ultraviolet-induced carcinogenesis, but increases tumor aggressiveness

AU - Brouxhon, Sabine

AU - Konger, Raymond L.

AU - VanBuskirk, Jo Anne

AU - Sheu, Tzong Jen

AU - Ryan, Julie

AU - Erdle, Brandon

AU - Almudevar, Anthony

AU - Breyer, Richard M.

AU - Scott, Glynis

AU - Pentland, Alice P.

PY - 2007/2/1

Y1 - 2007/2/1

N2 - Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE 2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP 2 -/- cells.

AB - Ultraviolet (UV) light is a complete carcinogen inducing and promoting squamous-cell carcinoma (SCC) of the skin. Recent work has shown that SCC initiation and promotion are enhanced by prostaglandin E2 (PGE 2). PGE2 interacts with specific EP receptors to regulate cellular functions. Previous work from our group has shown that the prostaglandin E2 EP2 receptor is a powerful regulator of keratinocyte growth. SKH-1 hairless mice lacking the EP2 receptor were therefore studied to understand how this growth signaling pathway contributes to photocarcinogenesis. Our data indicate that UV-irradiated mice lacking EP2 receptors exhibit decreased proliferation and a poor capacity for epidermal hypertrophy in response to UV injury. In a chronic irradiation model, these animals were protected from tumor formation, developing 50% fewer tumors than wild-type controls. Despite this capacity to protect against tumorigenesis, animals lacking EP2 receptors grew tumors that were larger in size, with a more aggressive phenotype. Further study suggested that this susceptibility may be associated with synthesis of active metalloproteinase enzymes in greater quantities than keratinocytes expressing the EP2 receptor, thereby enhancing the invasive potential of EP 2 -/- cells.

UR - http://www.scopus.com/inward/record.url?scp=33846292926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846292926&partnerID=8YFLogxK

U2 - 10.1038/sj.jid.5700547

DO - 10.1038/sj.jid.5700547

M3 - Article

C2 - 16977324

AN - SCOPUS:33846292926

VL - 127

SP - 439

EP - 446

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 2

ER -