|
|||||
|
|
Differential binding modes of the bromodomains of CREB-binding protein (CBP) and p300 with acetylated MyoD |
|
| Authors: | Wei Lanlan Jamonnak Nuttara Choy Jeremy Wang Zhenghe Zheng Weiping |
| Institution: | a Department of Internal Medicine, Division of Cardio-Vascular Medicine and Cardiovascular Research Institute, Kurume University School of Medicine, 67 Asahimachi, Kurume 830-0011, Japan b Department of Pediatrics, Kurume University School of Medicine, Kurume, Japan c Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan d Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan e Department of Cardiovascular Medicine, Kyushu University Graduate School of Medicine, Fukuoka, Japan f Department of Pharmaceutics, Inenaga Hospital, Chikuzen, Japan g Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan |
| Abstract: | We investigated whether blocking of monocyte chemoattractant-1 (MCP-1) function would inhibit recruitment of tumor-associated macrophages (TAMs) and prevent tumor angiogenesis and tumor growth of human malignant melanoma. B16-F1 melanoma cells were implanted onto the back of C57BL/6 mice (Day 0). At Day 7, a dominant negative MCP-1 mutant (7ND) gene was transfected in the thigh muscle to make overexpressed 7ND protein secreted into systemic circulation. 7ND treatment inhibited TAM recruitment and partially reduced tumor angiogenesis and tumor growth. Also, 7ND treatment attenuated inductions of tumor necrosis factor-α (TNFα), interleukin-1α (IL-1α), and vascular endothelial growth factor (VEGF) in the stroma and tumor. Melanoma cells expressed not only MCP-1 but also its receptor CCR2. Accordingly, it was suggested that MCP-1 would enhance tumor angiogenesis and early tumor growth in the early stages by inducing TNFα, IL-1α, and VEGF through TAM recruitment and probably the direct autocrine/paracrine effects on melanoma cells. |
| Keywords: | MCP-1 monocyte chemoattractant protein-1 7ND a dominant negative MCP-1 mutant lacking the N-terminal amino acids 2-8 TAM tumor-associated macrophage VEGF vascular endothelial growth factor IL-1α interleukin-1α TNFα tumor necrosis factor-α PCR recombinant polymerase chain reaction RT-PCR reverse-transcribed PCR |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |