Journal
EXPERIMENTAL CELL RESEARCH
Volume 319, Issue 8, Pages 1156-1164Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2013.02.007
Keywords
Fibroblast growth factor 8b; Phage display; Proliferation; Cell cycle; Prostate cancer
Categories
Funding
- National Natural Science Foundation of China [30973671, 81071800]
- Natural Science Foundation of Guangdong Province of China [9151064001000031]
- Science and Technology Planning Project of Wenzhou [Y20090244]
- Natural Science Foundation of Zhejiang Province of China [Y4090379, Y2110492]
- Guangdong Provincial Science and Technology Program [2010B060900040]
- Fundamental Research Funds for the Central Universities
- Guangdong Provincial Thousand-Hundred-Ten Talent Project
- Scientific Research Foundation for the Returned Overseas Chinese Scholars
- State Education Ministry
- Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Jinan University
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Fibroblast growth factor 8b (FGF8b) is the major isoform of FGF8 expressed in prostate cancer and it correlates with the stage and grade of the disease. FGF8b has been considered as a potential target for prostate cancer therapy. Here we isolated 12 specific FGF8b-binding phage clones by screening a phage display heptapeptide library with FGF8b. The peptide (HSQAAVP, named as P12) corresponding to one of these clones showed high homology to the immunoglobulin-like (Ig-like) domain II(D2) of high-affinity FGF8b receptor (FGFR3c), contained 3 identical amino acids (AVP) to the authentic FGFR3 D2 sequence aa 163-169 (LLAVPAA) directly participating in ligand binding, carried the same charges as its corresponding motif (aa163-169) in FGFR3c, suggesting that P12 may have a greater potential to interrupt FGF8b binding to its receptors than other identified heptapeptides do. Functional analysis indicated that synthetic P12 peptides mediate significant inhibition of FGF8b-induced cell proliferation, arrest cell cycle at the G0/G1 phase via suppression of Cyclin D1 and PCNA, and blockade of the activations of Erk1/2 and Akt cascades in both prostate cancer cells and vascular endothelial cells. The results demonstrated that the P12 peptide acting as an FGF8b antagonist may have therapeutic potential in prostate cancer. (c) 2013 Elsevier Inc. All rights reserved.
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