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

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

Immunohistochemical localization of selected pro-inflammatory factors in uterine myomas and myometrium in women of various ages

“…It was found that COX-2 prevented apoptosis and was associated with inflammation, cell growth and differentiation [5]. Prostaglandins produced via COX-2 activation, including prostaglandin E2 (PGE2), are believed to be the major contributors to cell proliferation [36], and PGE2 has been regarded as a primary COX-2 product in smooth muscle cells [37]. Transfection of rat intestinal epithelial cells with COX-2 gene caused inhibition of apoptosis accompanied by increased spontaneous output of PGE 2 and increased levels of an anti-apoptotic protein Bcl-2 [38].…”

Mitogen-activated Protein Kinase (MAPK) Activated by Prostaglandin E2 Phosphorylates Connexin 43 and Closes Osteocytic Hemichannels in Response to Continuous Flow Shear Stress

“…These results suggest that FFSS induces PGE 2 release and PGE 2 accumulates over time in the CM collected from continuous FFSS. PGE 2 is known to activate MAPK signaling through EP 2 or EP 4 receptors (27,28). Previous studies from our laboratory and others have shown that PGE 2 signaling occurs through EP 2 and EP4 receptors in MLO-Y4 osteocytes (5, 7).…”

Involvement of IGF binding protein 5 in prostaglandin E2-induced cellular senescence in human fibroblasts

“…1c) in a dose and timedependent manner. Since PGE 2 stimulates cell proliferation in vascular smooth muscle cells (Yau and Zahradka 2003) and esophageal cancer cells (Yu et al 2009), we treated cells with submicromolar concentrations of PGE 2 and measured cell proliferation by cell counting. No significant reduction or increase in cell proliferation was observed in cells treated with up to 1 lM PGE 2 (Fig.…”