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作者

Ren, ZJ Kang, WY Wang, LH Sun, BL Ma, JJ Zheng, CG Sun, J Tian, ZG Yang, XY Xiao, WH

作者单位

Univ Sci & Technol China, Med Ctr, Hefei 230027, Anhui, Peoples R China Weifang Med Coll, Affiliated Hosp, Weifang 261053, Shandong, Peoples R China Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China Univ Sci & Technol China, Sch Life Sci, Innovat Ctr Cell Biol, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China Taishan Med Coll, Tai An 271000, Shandong, Peoples R China

刊名

Molecular Cancer

年份

2014

卷号

Vol.13

ISSN

1476-4598

关键词

E2F1 ICAM-1 NF-kB Short hairpin RNA Tumor immunity

分类号

616.992

摘要

Background: E2F1 is the gatekeeper of the cell cycle controlling an analogous balance between proliferation and cell death. E2F1 expression is elevated in advanced prostate cancer. However, it is still unclear that the roles and mechanisms of E2F1 on prostate cancers. Methods: Targeted knockdown by interferon RNA was applied on two prostate cancer and Hela cell lines to examine the inverse correlation expression of E2F1 and ICAM-1. ICAM-1 promoter reporter and ChIP assays were used for analysis ...更多

Background: E2F1 is the gatekeeper of the cell cycle controlling an analogous balance between proliferation and cell death. E2F1 expression is elevated in advanced prostate cancer. However, it is still unclear that the roles and mechanisms of E2F1 on prostate cancers. Methods: Targeted knockdown by interferon RNA was applied on two prostate cancer and Hela cell lines to examine the inverse correlation expression of E2F1 and ICAM-1. ICAM-1 promoter reporter and ChIP assays were used for analysis of the molecular basis of transcriptional regulation of E2F1 on ICAM-1. Co-IP assays were employed for testing the protein interaction between E2F1 and NF-kB. Tumor xenograft mice model with E2F1 and ICAM-1-knockdown prostate cancer cells were used to investigate the effects of E2F1 and ICAM-1 on antitumor immunity. Results: E2F1 knockdown by a specific short hairpin RNA increased gene transcription and protein expression of ICAM-1. By using wild type and a series of mutant ICAM-1 promoter luciferase constructs, the NF-kB binding sites were found to be important for E2F1 regulation of ICAM-1 promoter. Targeted knockdown of E2F1 did not affect expression and phosphorylation of NF-kB and IkB alpha, but facilitated NF-kB binding to the ICAM-1 promoter, subsequently induced ICAM-1 transcription and production in prostate carcinoma cells. Furthermore, knockdown of E2F1 inhibited tumor growth of prostate cancer in vivo through increasing the susceptibility of tumor cells to ICAM-1-mediated anti-tumor immunity including enhancement of monocyte adhesion, leucocytes infiltration, as well as cytotoxicity against tumor cells. Conclusions: E2F1 knockdown inhibited prostate tumor growth in vitro and in vivo through sensitizing tumor cells to ICAM-1 mediated anti-immunity by NF-kB modulation, highlighting the potential of E2F1 as a therapeutic target.收起

学科

【SCI学科】BIOCHEMISTRY & MOLECULAR BIOLOGY;ONCOLOGY 【ESI学科】MOLECULAR BIOLOGY & GENETICS

影响因子

2016年:6.204;2015年:5.888;2014年:4.257;2013年:5.397;2012年:5.134

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