Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma

Erik G. Cohen; Taghreed Almahmeed; Baoheng Du; Dragan Golijanin; Jay O. Boyle; Robert A. Soslow; Kotha Subbaramaiah; Andrew J. Dannenberg

Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma

Erik G. Cohen, Taghreed Almahmeed, Baoheng Du, Dragan Golijanin, Jay O. Boyle, Robert A. Soslow, Kotha Subbaramaiah, Andrew J. Dannenberg

Research Institute

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Elevated levels of prostaglandin E₂ (PGE₂) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H₂ (PGH₂) to PGE₂. Given the apparent significance of PGE₂ in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE₂ in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE ₂ caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE₂ (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE₂ found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.

Original language	English (US)
Pages (from-to)	3425-3430
Number of pages	6
Journal	Clinical Cancer Research
Volume	9
Issue number	9
State	Published - Sep 1 2003

ASJC Scopus subject areas

Oncology
Cancer Research

Cite this

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title = "Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma",

abstract = "Elevated levels of prostaglandin E2 (PGE2) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H2 (PGH2) to PGE2. Given the apparent significance of PGE2 in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE2 in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE 2 caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE2 (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE2 found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.",

author = "Cohen, {Erik G.} and Taghreed Almahmeed and Baoheng Du and Dragan Golijanin and Boyle, {Jay O.} and Soslow, {Robert A.} and Kotha Subbaramaiah and Dannenberg, {Andrew J.}",

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T1 - Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma

AU - Cohen, Erik G.

AU - Almahmeed, Taghreed

AU - Du, Baoheng

AU - Golijanin, Dragan

AU - Boyle, Jay O.

AU - Soslow, Robert A.

AU - Subbaramaiah, Kotha

AU - Dannenberg, Andrew J.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - Elevated levels of prostaglandin E2 (PGE2) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H2 (PGH2) to PGE2. Given the apparent significance of PGE2 in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE2 in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE 2 caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE2 (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE2 found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.

AB - Elevated levels of prostaglandin E2 (PGE2) occur in head and neck squamous cell carcinoma (HNSCC) and have been associated with a poor prognosis. Recently, an inducible microsomal prostaglandin E synthase-1 (mPGES) was identified. This enzyme converts the cyclooxygenase product prostaglandin H2 (PGH2) to PGE2. Given the apparent significance of PGE2 in carcinogenesis, it is important to elucidate the mechanisms that account for increased amounts of PGE2 in HNSCC. By immunoblot analysis, mPGES was overexpressed in 11 of 14 (79%) cases of HNSCC compared with adjacent normal tissue. Immunohistochemistry localized mPGES expression to neoplastic epithelial cells. Cell culture was used to determine whether cellular transformation was associated with increased amounts of mPGES. Levels of mPGES protein and mRNA were markedly elevated in HNSCC cell lines (1483 and Ca9-22) versus a nontumorigenic oral epithelial cell line (MSK-Leuk1). Interestingly, treatment of MSK-Leuk1 cells with PGE 2 caused both dose- and time-dependent stimulation of cell growth. Each of the four known receptors for PGE2 (E-prostanoid receptor subtypes 1-4) was detected in head and neck squamous mucosa. Taken together, these results suggest that overexpression of mPGES contributes to the increased levels of PGE2 found in HNSCC. Additional studies will be needed to determine whether this enzyme is a bona fide target for anticancer therapy.

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Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma

Abstract

ASJC Scopus subject areas

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