Abstract |
The fibroblast growth factors (FGFs) are important for embryo development, wound healing, hematopoiesis, and angiogenesis. FGF-1, a member of FGF family, is involved in both receptor-dependent pathways and an intracrine pathway. Studies have recently shown that FGF-1 is overexpressed in the early stages of several kinds of cancer. Thus, FGF-1 is a candidate for cancer immunotargeting. To study the potential use of therapeutic antibodies against FGF-1, a monoclonal hybridoma 1C9 secreting monoclonal antibody specific for FGF-1 was developed. Then, a single-chain variable fragment (scFv) antibody was genetically engineered from hybridama 1C9. The binding of the scFv1C9 to the antigen FGF-1 was demonstrated by ELISA and immunoprecipitation assays. Functional analysis showed that the overexpressed scFv1C9 in MCF-7 cells targeted endogenous FGF-1 and prevented the translocation of FGF-1 into the nucleus, resulting in the blockade of the intracrine pathway of FGF-1, which caused the G1 arrest by p21 up-regulation. These results suggest that the generated scFv1C9 is an effective inhibitor of the intracrine pathway of FGF-1 and has a potential application as anti-tumoral agent in breast cancer.
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Authors | Heng-Liang Shi, Tao Yang, Khalissa Deffar, Chun-Guang Dong, Jing-Ying Liu, Chun-Ling Fu, Da-Xue Zheng, Bo Qin, Jun-Jie Wang, Xing-Zhi Wang, Xiao-Juan Zhu |
Journal | IUBMB life
(IUBMB Life)
Vol. 63
Issue 2
Pg. 129-37
(Feb 2011)
ISSN: 1521-6551 [Electronic] England |
PMID | 21360642
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Wiley Periodicals, Inc. |
Chemical References |
- Antineoplastic Agents
- Biomarkers, Tumor
- CDKN1A protein, human
- Cyclin-Dependent Kinase Inhibitor p21
- Recombinant Proteins
- Single-Chain Antibodies
- Fibroblast Growth Factor 1
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Topics |
- Animals
- Antineoplastic Agents
(immunology, pharmacology, therapeutic use)
- Base Sequence
- Biomarkers, Tumor
(genetics, metabolism)
- Breast Neoplasms
(drug therapy, genetics, immunology, metabolism, pathology)
- Cell Cycle
(drug effects)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin-Dependent Kinase Inhibitor p21
(genetics, metabolism)
- Escherichia coli
- Female
- Fibroblast Growth Factor 1
(genetics, metabolism)
- Gene Expression
- Humans
- Hybridomas
(chemistry, metabolism)
- Immunomodulation
- Mice
- Molecular Sequence Data
- Molecular Targeted Therapy
(methods)
- Recombinant Proteins
(genetics, metabolism)
- Signal Transduction
(drug effects)
- Single-Chain Antibodies
(immunology, pharmacology, therapeutic use)
- Up-Regulation
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