Microsomal prostaglandin E synthase-1 is overexpressed in head and neck squamous cell carcinoma Journal Article
| Authors: | Cohen, E. G.; Almahmeed, T.; Du, B.; Golijanin, D.; Boyle, J. O.; Soslow, R. A.; Subbaramaiah, K.; Dannenberg, A. J. |
| Article 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. |
| Keywords: | immunohistochemistry; controlled study; human tissue; unclassified drug; human cell; squamous cell carcinoma; carcinoma, squamous cell; comparative study; protein blood level; gene overexpression; reverse transcription polymerase chain reaction; cell line; cancer cell culture; enzyme activity; time factors; carcinogenesis; cell transformation, neoplastic; blotting, western; reverse transcriptase polymerase chain reaction; head and neck neoplasms; rna, messenger; cell transformation; prostanoid receptor; immunoblotting; thiazoles; prostaglandin e; enzyme localization; head and neck carcinoma; mucous membrane; intramolecular oxidoreductases; tetrazolium salts; coloring agents; prostaglandin e receptor; prostaglandin synthase; microsome; microsomes; humans; prognosis; human; priority journal; article; microsomal prostaglandin e synthase 1 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 9 |
| Issue: | 9 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2003-08-15 |
| Start Page: | 3425 |
| End Page: | 3430 |
| Language: | English |
| PUBMED: | 12960132 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
