Research article summary (published 29 Nov 2009):

Prostaglandin E(2) 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.

Full 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.

Author information

Author/s: Yu, Le (L); Wu, William Ka Kei (WK); Li, Zhi Jie (ZJ); Li, Hai Tao (HT); Wu, Ya Chun (YC); Cho, Chi Hin (CH);

Affiliation: Department of Pharmacology, The Chinese University of Hong Kong, Hong Kong, China.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Dec; vol 125 (issue 11) : pp 2540-6

Dates: Created 2009/10/05; Completed 2009/11/06;

PMID: 19623651, status: MEDLINE (last retrieval date: 11/6/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Blotting, Western Carcinoma, Squamous Cell - genetics; metabolism; pathology Cell Proliferation Cyclooxygenase 2 - metabolism Dinoprostone - pharmacology Esophageal Neoplasms - genetics; metabolism; pathology Extracellular Signal-Regulated MAP Kinases - metabolism Fluorescent Antibody Technique Humans Immunoprecipitation

Immunoprecipitation Oxytocics - pharmacology Phosphorylation Protein Kinase C - metabolism Proto-Oncogene Proteins c-myc - antagonists & inhibitors; genetics; metabolism RNA, Messenger - genetics; metabolism RNA, Small Interfering - pharmacology Receptors, Prostaglandin E - antagonists & inhibitors; genetics; metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction

Associated Chemicals: MYC protein, human (0) ; Oxytocics (0) ; Proto-Oncogene Proteins c-myc (0) ; RNA, Messenger (0) ; RNA, Small Interfering (0) ; Receptors, Prostaglandin E (0) ; prostaglandin EP2 receptor (0) ; Dinoprostone (363-24-6) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.1.37) ; Protein Kinase C (EC 2.7.11.13)

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