This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ozaki, I. Articles by Yamamoto, K. Search for Related Content PubMed PubMed Citation Articles by Ozaki, I. Articles by Yamamoto, K.

Involvement of the Ets-1 Gene in Overexpression of Matrilysin in Human Hepatocellular Carcinoma¹

Health Administration Center [I. O.] and Department of Internal Medicine [T. M., G. Z., H. Y., T. H., S. K., A. H., K. Y.], Saga Medical School, Saga 849-8501, and Musashino Red Cross Hospital, Musashino, Tokyo 180-0023 [T. S.], Japan

Although matrix metalloproteinases (MMPs) are thought to be involved in the invasion and metastasis of a variety of malignant tumors, including human hepatocellular carcinoma (HCC), the mechanisms for the expression of MMPs in HCC are not known. To understand the mechanism(s) of MMP expression, the expression of matrilysin (MMP-7) and several genes of the Ets transcription factor family was investigated in human HCC and hepatoma-derived cell lines. The role of Ets-1 gene expression in HCC was also studied. Analysis by semiquantitative reverse transcription-PCR revealed that MMP-7 and Ets-1 are overexpressed and closely associated in HCC. To clarify the role of Ets-1, hepatoma cells were transduced with human Ets-1 or targeted with the Ets-1-specific antisense oligonucleotides. Cells stably transduced with the Ets-1 gene showed increased MMP-7 expression compared to parental and mock-transfected cells. Cells targeted with Ets-1-specific antisense oligonucleotides showed reduced expression of MMP-7. Cotransfection of cells with a MMP-7 promoter-reporter gene plasmid and an Ets-1 expression vector yielded an increase in MMP-7 promoter activity in an Ets-1-responsive element-dependent manner. Taken together, these data suggested that the Ets-1 oncogene is up-regulated and involved in the overexpression of MMP-7 in human HCC and may contribute to the progression of HCC.

This article has been cited by other articles:

				I. Ozaki, H. Zhang, T. Mizuta, Y. Ide, Y. Eguchi, T. Yasutake, T. Sakamaki, R. G. Pestell, and K. Yamamoto Menatetrenone, a Vitamin K2 Analogue, Inhibits Hepatocellular Carcinoma Cell Growth by Suppressing Cyclin D1 Expression through Inhibition of Nuclear Factor {kappa}B Activation Clin. Cancer Res., April 1, 2007; 13(7): 2236 - 2245. [Abstract] [Full Text] [PDF]

				N. Lasagna, O. Fantappie, M. Solazzo, L. Morbidelli, S. Marchetti, G. Cipriani, M. Ziche, and R. Mazzanti Hepatocyte growth factor and inducible nitric oxide synthase are involved in multidrug resistance-induced angiogenesis in hepatocellular carcinoma cell lines. Cancer Res., March 1, 2006; 66(5): 2673 - 2682. [Abstract] [Full Text] [PDF]

				H. Yamamoto, S. Horiuchi, Y. Adachi, H. Taniguchi, K. Nosho, Y. Min, and K. Imai Expression of ets-related transcriptional factor E1AF is associated with tumor progression and over-expression of matrilysin in human gastric cancer Carcinogenesis, March 1, 2004; 25(3): 325 - 332. [Abstract] [Full Text] [PDF]

				B. Burke, A. Giannoudis, K. P. Corke, D. Gill, M. Wells, L. Ziegler-Heitbrock, and C. E. Lewis Hypoxia-Induced Gene Expression in Human Macrophages: Implications for Ischemic Tissues and Hypoxia-Regulated Gene Therapy Am. J. Pathol., October 1, 2003; 163(4): 1233 - 1243. [Abstract] [Full Text] [PDF]

				E. Aklillu, J. A. Carrillo, E. Makonnen, K. Hellman, M. Pitarque, L. Bertilsson, and M. Ingelman-Sundberg Genetic Polymorphism of CYP1A2 in Ethiopians Affecting Induction and Expression: Characterization of Novel Haplotypes with Single-Nucleotide Polymorphisms in Intron 1 Mol. Pharmacol., September 1, 2003; 64(3): 659 - 669. [Abstract] [Full Text] [PDF]

				J. Fujimoto, I. Aoki, H. Toyoki, S. Khatun, and T. Tamaya Clinical implications of expression of ETS-1 related to angiogenesis in uterine cervical cancers Ann. Onc., October 1, 2002; 13(10): 1598 - 1604. [Abstract] [Full Text] [PDF]

				J. Fujimoto, I. Aoki, H. Toyoki, S. Khatun, and T. Tamaya Clinical implications of expression of ETS-1 related to angiogenesis in uterine endometrial cancers Ann. Onc., October 1, 2002; 13(10): 1605 - 1611. [Abstract] [Full Text] [PDF]

				C. Wasylyk, S. E. Schlumberger, P. Criqui-Filipe, and B. Wasylyk Sp100 Interacts with ETS-1 and Stimulates Its Transcriptional Activity Mol. Cell. Biol., April 15, 2002; 22(8): 2687 - 2702. [Abstract] [Full Text] [PDF]

				H. Fukushima, H. Yamamoto, F. Itoh, H. Nakamura, Y. Min, S. Horiuchi, S. Iku, S. Sasaki, and K. Imai Association of matrilysin mRNA expression with K-ras mutations and progression in pancreatic ductal adenocarcinomas Carcinogenesis, July 1, 2001; 22(7): 1049 - 1052. [Abstract] [Full Text] [PDF]