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Molecules 2014, 19(12), 20768-20779; doi:10.3390/molecules191220768

Up-Regulation of Urotensin II and Its Receptor Contributes to Human Hepatocellular Carcinoma Growth via Activation of the PKC, ERK1/2, and p38 MAPK Signaling Pathways

1
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing 100069, China
2
Department of Pathology, Peking Union Medical Hospital, Beijing 100692, China
3
Department of General Surgery, Beijing Jishuitan Hospital, Beijing 100031, China
4
Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
*
Authors to whom correspondence should be addressed.
Received: 17 September 2014 / Revised: 27 November 2014 / Accepted: 5 December 2014 / Published: 12 December 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Urotensin II (UII) and its receptor (UTR) have mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UTR system is up-regulated in dithyinitrosamine-induced precancerous rat liver lesions. However, its role in human hepatocellular carcinoma remains unknown. In this study, the mRNA and protein expression of UII and its receptor (UTR) in human hepatocellular carcinoma samples and in the BEL-7402 human hepatoma cell line were evaluated. In addition, the effect of exogenous UII on the pathways that regulate proliferation in BEL-7402 cells in vitro were determined. Liver sections were subjected to immunohistochemical staining. mRNA expression was detected by real-time polymerase chain reaction analysis, and protein levels were evaluated by western blotting. Proliferating cells were detected by BrdU incorporation. The expression of UII/UT mRNA and protein significantly increased in human hepatocellular carcinoma samples, and in BEL-7402 cells. Administration with UII increased the phosphorylation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, GF109203x, PD184352, and SB203580 partially abolished UII-induced proliferation of BEL-7402 cells. These results provide the first evidence that up-regulation of the UII/UT system may enhance proliferation of the human hepatoma cell line at least in part via PKC, ERK1/2, and p38 MAPK signaling pathways, and may provide novel therapeutic targets for inhibiting human hepatocellular carcinoma. View Full-Text
Keywords: urotensin II; human hepatocellular carcinoma; cell proliferation; signaling pathway urotensin II; human hepatocellular carcinoma; cell proliferation; signaling pathway
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Yu, X.-T.; Wang, P.-Y.; Shi, Z.-M.; Dong, K.; Feng, P.; Wang, H.-X.; Wang, X.-J. Up-Regulation of Urotensin II and Its Receptor Contributes to Human Hepatocellular Carcinoma Growth via Activation of the PKC, ERK1/2, and p38 MAPK Signaling Pathways. Molecules 2014, 19, 20768-20779.

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