Potential role of microsomal prostaglandin E synthase-1 in tumorigenesis

被引:177
作者
Kamei, D
Murakami, M
Nakatani, Y
Ishikawa, Y
Ishii, T
Kudo, I
机构
[1] Showa Univ, Sch Pharmaceut Sci, Dept Hlth Chem, Shinagawa Ku, Tokyo 1428555, Japan
[2] Toho Univ, Sch Med, Dept Pathol, Ohta Ku, Tokyo 1438540, Japan
关键词
D O I
10.1074/jbc.M213290200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Microsomal prostaglandin E-2 synthase-1 (mPGES-1) is a stimulus-inducible enzyme that functions downstream of cyclooxygenase ( COX)-2 in the PGE(2)-biosynthetic pathway. Given the accumulating evidence that COX-2-derived PGE(2) participates in the development of various tumors, including colorectal cancer, we herein examined the potential involvement of mPGES-1 in tumorigenesis. Immunohistochemical analyses demonstrated the expression of both COX-2 and mPGES-1 in human colon cancer tissues. HCA-7, a human colorectal adenocarcinoma cell line that displays COX-2- and PGE(2)-dependent proliferation, expressed both COX-2 and mPGES-1 constitutively. Treatment of HCA-7 cells with an mPGES-1 inhibitor or antisense oligonucleotide attenuated, whereas overexpression of mPGES-1 accelerated, PGE2 production and cell proliferation. Moreover, cotransfection of COX-2 and mPGES-1 into HEK293 cells resulted in cellular transformation manifested by colony formation in soft agar culture and tumor formation when implanted subcutaneously into nude mice. cDNA array analyses revealed that this mPGES-1-directed cellular transformation was accompanied by changes in the expression of a variety of genes related to proliferation, morphology, adhesion, and the cell cycle. These results collectively suggest that aberrant expression of mPGES-1 in combination with COX-2 can contribute to tumorigenesis.
引用
收藏
页码:19396 / 19405
页数:10
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