Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis

	Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis
	Zou, L; Yang, RX; Chai, JJ; Pei, G
刊名	FASEB JOURNAL
	2008
卷号	22 期号:2 页码:355-364
关键词	matrix metalloproteinase 9 MMP9 vascular endothelial growth factor VEGF phosphatidylinositol 3-kinase PI3K
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China.,gpei@sibs.ac.cn
英文摘要	beta-arrestins (beta-Arrs) are known to be associated with tumor signaling pathways such as transforming growth factor-beta 1 (TGF-beta 1), P53/Murine double minute (MDM2) and NF-kappa B. To investigate the role of beta-Arr in tumor progression in vivo, we generated beta-Arr transgenic mice by subcutaneously inoculating tumor cells in them. We found that the xenograft tumor initiated earlier and grew more rapidly in beta-Arr1 transgenic mice than in both the beta-Arr2 transgenic and wild-type mice after inoculating murine liver cancer Hepa1-6 cells or lymphoma EL4 cells. Moreover, matrix metalloproteinase 9 (MMP9) activity, vascular endothelial growth factor ( VEGF) concentration in plasma and new small blood vessel formation in tumor tissues were enhanced in beta-Arr1 transgenic mice compared with those in control mice. In addition, injection of MMP9 inhibitors in beta-Arr1 transgenic mice abrogated all these effects and suppressed rapid tumor progression. Similar results were observed in human microvascular endothelial cells, where overexpressed beta-Arr1 did increase MMP9 activity and small blood vessel formation. Furthermore, phosphatidylinositol 3-kinase (PI3K) inhibitors could suppress beta-Arr1-enhanced MMP9 activity and the C-terminal 181-418 amino acids (aa) of beta-Arr1 was largely responsible for this effect. Our data reveal a functional role for beta-arrestin1 in tumor progression in vivo, in which overexpression of beta-Arr1 promotes MMP9 activity and tumor angiogenesis by providing a suitable microenvironment for tumor progression.
学科主题	Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Biology ; Cell Biology
关键词[WOS]	ARRESTIN-DEPENDENT ENDOCYTOSIS ; PROTEASE-ACTIVATED RECEPTOR-2 ; GROWTH-FACTOR VEGF ; BETA-ARRESTIN ; MATRIX METALLOPROTEINASES ; PHOSPHATIDYLINOSITOL 3-KINASE ; OVARIAN-CARCINOMA ; CANCER-THERAPY ; GELATINASE-B ; CELL-LINE
收录类别	SCI
语种	英语
WOS记录号	WOS:000252822600005
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1342]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zou, L,Yang, RX,Chai, JJ,et al. Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis[J]. FASEB JOURNAL,2008,22(2):355-364.
APA	Zou, L,Yang, RX,Chai, JJ,&Pei, G.(2008).Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis.FASEB JOURNAL,22(2),355-364.
MLA	Zou, L,et al."Rapid xenograft tumor progression in beta-arrestin1 transgenic mice due to enhanced tumor angiogenesis".FASEB JOURNAL 22.2(2008):355-364.