RGD Reference Report - Expression of COX-2 is associated with accumulation of p53 in pancreatic cancer: analysis of COX-2 and p53 expression in premalignant and malignant ductal pancreatic lesions. - Rat Genome Database

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Expression of COX-2 is associated with accumulation of p53 in pancreatic cancer: analysis of COX-2 and p53 expression in premalignant and malignant ductal pancreatic lesions.

Authors: Hermanova, M  Trna, J  Nenutil, R  Dite, P  Kala, Z 
Citation: Hermanova M, etal., Eur J Gastroenterol Hepatol. 2008 Aug;20(8):732-9.
RGD ID: 2317186
Pubmed: PMID:18617777   (View Abstract at PubMed)
DOI: DOI:10.1097/MEG.0b013e3282f945fb   (Journal Full-text)

OBJECTIVES: Cyclooxygenase-2 (COX-2) and tumor suppressor p53 are molecules that are linked to the oncogenesis of pancreatic cancer. COX-2 represents a key modulatory molecule in inflammation and carcinogenesis, and is known to be implicated in the positive regulation of growth and tumorigenesis. Abnormal expression of p53 is common in many human neoplasms including pancreatic cancer. Recent studies demonstrated functional interactions between p53 and COX-2. The p53-dependent upregulation of COX-2 was proposed to be another mechanism by which p53 could abate its own growth-inhibitory and apoptotic effects. METHODS: In this study, we immunohistochemically analyzed the expression of COX-2 and p53 in 95 pancreatic resection specimens [adenocarcinomas, 95 lesions; pancreatic intraepithelial neoplasias (PanINs), 155; normal ducts, 70]. RESULTS: The expression of COX-2 increased progressively with the grade of ductal lesions (P<0.00001). A statistically significant difference of COX-2 expression between normal ducts and low-grade PanINs was revealed (P=0.0042). COX-2 overexpression was demonstrated in 82 PanINs (52.9%), and in 76 adenocarcinomas (80%). No significant correlation between the grade of adenocarcinoma and COX-2 expression was revealed (P=0.2). The expression of p53 again increased progressively with the grade of lesions (P<0.00001) with a significant increase in high-grade PanINs. A correlation between COX-2 and p53 expression levels in carcinomas was revealed (P=0.0002), and an accumulation of p53 was associated with COX-2 overexpression in premalignant and malignant ductal lesions. CONCLUSION: These findings confirmed the generally accepted pancreatic cancer progression model, and supported the concept of the interactive role of COX-2 and p53 in pancreatic cancer carcinogenesis, which offers opportunities for targeted therapy and chemoprevention of pancreatic cancer using COX-2 inhibitors.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGS2Humanin situ carcinoma  IEP protein:increased expression:pancreasRGD 
Ptgs2Ratin situ carcinoma  ISOPTGS2 (Homo sapiens)protein:increased expression:pancreasRGD 
Ptgs2Mousein situ carcinoma  ISOPTGS2 (Homo sapiens)protein:increased expression:pancreasRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information