HIV-Tat-Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells

	HIV-Tat-Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells
	Chen, GM; Da, LA; Wang, HF; Xu, Y; Chen, GY; Sun, CF; Wang, LM; Zhao, J; Zhang, F; Feng, JA
刊名	GASTROENTEROLOGY
	2011
卷号	140 期号:1 页码:332-343
关键词	Recombinant Protein Telomerase Inhibitor Liver Cancer Protein Therapy
通讯作者	Zhao, MJ (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, State Key Lab Mol Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China.,mjzhao@sibs.ac.cn
英文摘要	BACKGROUND & AIMS: Human liver-related putative tumor suppressor (LPTS) is a gene that encodes a telomerase inhibitory protein that is similar to human Pin2/TRF1-interacting protein. The LPTS protein binds directly to the telomerase catalytic subunit (human telomerase reverse transcriptase) and suppresses telomerase activity. Telomere maintenance and telomerase activity are required for long-term proliferation of cancer cells, so LPTS might be used in anticancer strategies. METHODS: The carboxy-terminal (functional) fragment of LPTS was fused to the transactivator of transcription of human immunodeficiency virus (Tat)-an 11-amino acid peptide that translocates across the cell membrane; the TAT-fused C-terminal of LPTS (TAT-LPTS-LC) was purified and transduced into cells. Telomerase activity was identified by using the telomeric repeat amplification protocol. The effects of the TAT-LPTS-LC protein on cell proliferation and death were evaluated by colorimetric tetrazolium salt and flow cytometry analyses. Tumor growth was analyzed in nude mice. RESULTS: The purified TAT-LPTS-LC protein was efficiently delivered into the cells, where it suppressed telomerase activity and shortened telomere length. TAT-LPTS-LC inhibited proliferation of telomerase-positive hepatocellular carcinoma BEL-7404 and hepatoblastoma HepG2cells and induced their death; however, it had no effect on telomerase-negative liver cell line L02 and osteosarcoma cell line Saos-2. In mice, tumor formations by BEL-7404 cells were suppressed by TAT-LPTS-LC treatments. CONCLUSIONS: Transduction of hepatoma cells with a fusion protein that contains the C-terminal, functional fragment of LPTS and human immunodeficiency virus Tat (TAT-LPTS-LC) causes telomere shortening, limits proliferation, and inhibits growth of tumors from these cells in mice. TAT-LPTS-LC inhibits telomerase activity and might be developed as an anticancer agent.
学科主题	Gastroenterology & Hepatology
类目[WOS]	Gastroenterology & Hepatology
关键词[WOS]	PUTATIVE-TUMOR-SUPPRESSOR ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; GENE ; HETEROZYGOSITY ; LOCI ; IDENTIFICATION ; CHROMOSOME-8 ; SENESCENCE ; DISEASE
收录类别	SCI
语种	英语
WOS记录号	WOS:000285503200048
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/729]
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	Chen, GM,Da, LA,Wang, HF,et al. HIV-Tat-Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells[J]. GASTROENTEROLOGY,2011,140(1):332-343.
APA	Chen, GM.,Da, LA.,Wang, HF.,Xu, Y.,Chen, GY.,...&Zhao, MJ.(2011).HIV-Tat-Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells.GASTROENTEROLOGY,140(1),332-343.
MLA	Chen, GM,et al."HIV-Tat-Mediated Delivery of an LPTS Functional Fragment Inhibits Telomerase Activity and Tumorigenicity of Hepatoma Cells".GASTROENTEROLOGY 140.1(2011):332-343.