Amphiregulin as a tumor promoter for oral squamous cell carcinoma: involvement of cyclooxygenase 2.

Abstract	Amphiregulin (AR), an epidermal growth factor (EGF)-like molecule, is a mitogen for keratinocytes. Squamous cell carcinoma (SCC) is a tumor derived from keratinoctyes. Expression of AR mRNA positively correlated with the clinical progression of 39 oral SCC. Oral SCC line, KB, was used as a model to study if increased expression of AR altered the biological behaviors of SCC cells. Exogenous AR dose-dependently enhanced the proliferation of KB cells expressing EGF receptor 1 (EGFR-1), a major receptor for AR, but little AR. Neutralizing anti-AR antibody significantly reversed the stimulatory effect of exogenous AR on KB cell proliferation. Ectopically expressed AR in stable clones manifested higher abilities to proliferate, migrate and invade Matrigel than vector control. Cyclooxygenase 2 (COX-2), but not metalloprotease 9 (MMP-9) mRNA, was increased in all the AR-expressing stable clones. In summary, AR behaves as a tumor promoter for oral SCC cells partly via increased expression of COX-2.
Authors	Sen-Tien Tsai, Kai-Ying Yang, Ying-Tai Jin, Yen-Chun Lin, Mei-Tzu Chang, Li-Wha Wu
Journal	Oral oncology (Oral Oncol) Vol. 42 Issue 4 Pg. 381-90 (Apr 2006) ISSN: 1368-8375 [Print] England
PMID	16376136 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	AREG protein, human Amphiregulin Areg protein, mouse Carcinogens EGF Family of Proteins Glycoproteins Intercellular Signaling Peptides and Proteins Neoplasm Proteins RNA, Messenger RNA, Neoplasm Cyclooxygenase 2
Topics	Amphiregulin Animals Blotting, Western Carcinogens Carcinoma, Squamous Cell (etiology, metabolism, pathology) Cell Division Cell Transformation, Neoplastic Cyclooxygenase 2 (physiology) EGF Family of Proteins Glycoproteins (antagonists & inhibitors, pharmacology, physiology) Humans Intercellular Signaling Peptides and Proteins (pharmacology, physiology) Keratinocytes (metabolism, pathology) Mice Mouth Neoplasms (etiology, pathology) Neoplasm Proteins (physiology) Phosphorylation RNA, Messenger (metabolism) RNA, Neoplasm (metabolism) Reverse Transcriptase Polymerase Chain Reaction Tumor Cells, Cultured

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