Prostaglandin E2 promotes cell proliferation via protein kinase C/extracellular signal regulated kinase pathway-dependent induction of c-Myc expression in human esophageal squamous cell carcinoma cells

✍ Scribed by Le Yu; William Ka Kei Wu; Zhi Jie Li; Hai Tao Li; Ya Chun Wu; Chi Hin Cho

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 392 KB
• Volume: 125
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.24607

✦ Synopsis

Abstract

Overexpression of cyclooxygenase‐2 (COX‐2) and elevation of its derivative prostaglandin E~2~ (PGE~2~) are implicated in human esophageal squamous cell carcinoma. The expression of c‐Myc, an oncogenic transcription factor, is also upregulated in this malignant disease. This study sought to elucidate whether a functional connection exists between COX‐2/PGE~2~ and c‐Myc in esophageal squamous cell carcinoma. Results showed that PGE~2~ substantially increased the proliferation of cultured esophageal squamous cell carcinoma cells. In this regard, PGE~2~ substantially increased the mRNA and protein expression of c‐Myc and its association with the binding partner Max. Knockdown of c‐Myc by RNA interference also significantly attenuated PGE~2~‐induced cell proliferation. Further, mechanistic study revealed that PGE~2~ increased the protein stability and nuclear accumulation of c‐Myc via phosphorylation on serine 62 in an extracellular signal regulated kinase (ERK)‐dependent manner. To this end, ERK activation by PGE~2~ was completely abolished by protein kinase C (PKC) inhibitors. Moreover, the effect of PGE~2~ on c‐Myc expression was mimicked by EP2 receptor agonist. In addition, knockdown of EP2 receptor by EP2 siRNA attenuated PGE~2~‐induced c‐Myc expression. Collectively, our findings suggest that PGE~2~ upregulates c‐Myc via the EP2/PKC/ERK pathway. This study sheds new light on the carcinogenic mechanism of PGE~2~ in esophageal squamous cell carcinoma. © 2009 UICC