Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis Journal Article
| Authors: | Golijanin, D.; Tan, J. Y.; Kazior, A.; Cohen, E. G.; Russo, P.; Dalbagni, G.; Auborn, K. J.; Subbaramaiah, K.; Dannenberg, A. J. |
| Article Title: | Cyclooxygenase-2 and microsomal prostaglandin E synthase-1 are overexpressed in squamous cell carcinoma of the penis |
| Abstract: | Purpose: Prostaglandin E2 (PGE2) promotes malignant growth. Cyclooxygenase (COX) catalyzes the synthesis of PGH2, which is converted, in turn, by microsomal prostaglandin E synthase (mPGES-1) to PGE2. One strategy for inhibiting carcinogenesis is to prevent PGE2 production in premalignant and malignant tissues. It is important, therefore, to determine whether enzymes involved in PGE2 biosynthesis are deregulated in neoplasia. The main purpose of this study was to determine whether amounts of COX-2 or mPGES-1 were increased in intraepithelial neoplasia or squamous cell carcinoma (SCC) of the penis. Because human papillomavirus (HPV) has been linked to the development of penile SCC, a secondary objective was to determine whether COX-2 was overexpressed in SCC arising in an HPV16 transgenic mouse. Experimental Design: Immunohistochemistry and immunoblotting were used to evaluate the expression of COX-2 and mPGES-1 in benign and malignant lesions including metastases to lymph nodes. Amounts of intratumoral PGE2 were quantified by enzyme immunoassay. Reverse transcription-PCR was used to determine the expression of each of the four known receptors (EP1-4) for PGE2. Results: Immunohistochemistry demonstrated increased expression of COX-2 and mPGES-1 in dysplasia, carcinoma in situ, invasive SCC, and metastases to lymph nodes. Immunoblot analysis confirmed that COX-2 and mPGES-1 were consistently overexpressed in SCC. PGE2 and all four of the PGE2 receptor subtypes were detected in each of the tumor samples. Elevated levels of COX-2 were also detected in SCC arising in an HPV16 transgenic mouse. Conclusions: Increased amounts of COX-2 and mPGES-1 were detected in penile intraepithelial neoplasia and carcinoma. These findings provide the basis for evaluating whether inhibiting COX-2 will be useful in the prevention or treatment of penile SCC. |
| Keywords: | immunohistochemistry; clinical article; controlled study; human tissue; unclassified drug; human cell; squamous cell carcinoma; carcinoma, squamous cell; cancer growth; nonhuman; lymph node metastasis; animal cell; mouse; animals; mice; animal tissue; gene overexpression; reverse transcription polymerase chain reaction; animal model; membrane proteins; mice, transgenic; cancer inhibition; blotting, western; gene expression regulation, neoplastic; enzyme analysis; cyclooxygenase 2; carcinoma in situ; neoplasm metastasis; immunoblotting; penis carcinoma; penile neoplasms; catalysis; isoenzymes; enzyme synthesis; papilloma virus; intramolecular oxidoreductases; prostaglandin synthesis; dinoprostone; papillomaviridae; prostaglandin e receptor; quantitative diagnosis; prostaglandin synthase; prostaglandin-endoperoxide synthases; microsomes; humans; human; male; priority journal; article; prostaglandin 3 synthase 1 |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 3 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-02-01 |
| Start Page: | 1024 |
| End Page: | 1031 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-1032-3 |
| PROVIDER: | scopus |
| PUBMED: | 14871981 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):53 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
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