Disease relevance of FGFBP1

• FGF-BP is expressed at high levels in squamous cell carcinoma (SCC) cell lines and tumor samples and has been shown to be rate-limiting for the growth of SCC tumors in vivo [1].
• The fibroblast growth factor-binding protein (FGF-BP) stimulates FGF-2-mediated angiogenesis and is thought to play an important role in the progression of squamous cell, colon, and breast carcinomas [2].
• Here we demonstrate that the stable expression of the E6 oncogene of HPV 16 leads to an activation of the FGF-BP promoter in primary human foreskin keratinocytes (one of the natural host cells of these viruses) [3].
• Fibroblast growth factor-binding protein expression changes with disease progression in clinical and experimental human squamous epithelium [4].
• Complex regulation of the fibroblast growth factor-binding protein in MDA- MB-468 breast cancer cells by CCAAT/enhancer-binding protein beta [5].

High impact information on FGFBP1

• We propose that the up-regulation of the secreted FGF-BP1 protein during initiation of pancreas and colon neoplasia could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions [6].
• We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP1) as a chaperone molecule, which enhances the biological functions of FGFs by releasing FGFs from the extracellular matrix [6].
• Expression of a fibroblast growth factor-binding protein during the development of adenocarcinoma of the pancreas and colon [6].
• Here, we characterize the frequency and pattern of FGF-BP1 expression during the malignant progression of pancreas and colorectal carcinoma [6].
• For this, we generated monoclonal antibodies that detect FGF-BP1 protein in formalin-fixed, paraffin-embedded tissues and applied in situ hybridization to detect FGF-BP1 mRNA in adjacent tissue sections [6].

Biological context of FGFBP1

• We found that EGF treatment of the ME-180 SCC cell line caused a rapid induction of FGF-BP gene expression [1].
• This induction was mediated transcriptionally through the AP-1 (c-Fos/JunD) and CCAAT/enhancer-binding protein elements as well as through an E-box repressor site in the proximal regulatory region of the FGF-BP promoter [1].
• In this study, we examine the regulation of FGF-BP by epidermal growth factor (EGF) and the signal transduction mechanisms that mediate this effect [1].
• Mitogen-induced expression of the fibroblast growth factor-binding protein is transcriptionally repressed through a non-canonical E-box element [2].
• Transient E6 expression revealed that the observed activation of the FGF-BP promoter by the viral oncogene is an early process which is independent from immortalization/transformation events in the cells [3].

Anatomical context of FGFBP1

• Fibroblast growth factor-binding protein (FGF-BP) 1 is a secreted protein that can bind fibroblast growth factors (FGFs) 1 and 2 [7].
• In the present study co-localization of FGF-2 and HBp17/FGFBP-1 was observed in oral tissues including normal mucosa, hyperplasia, dysplasia of different degrees and oral squamous cell carcinoma (OSCC) [8].
• We demonstrate here that TGF-beta signaling significantly represses FGF-BP1 expression in mesenchymal and neural crest cells undergoing in vitro smooth muscle differentiation [9].

Associations of FGFBP1 with chemical compounds

• Differential regulation of a fibroblast growth factor-binding protein by receptor-selective analogs of retinoic acid [10].
• To further examine the mechanism of regulation of FGF-BP by retinoids and the role played by retinoid receptor subtypes, we utilized retinoic acid receptor (RAR)-selective (TTNPB) and retinoid X receptor (RXR)-selective (LG100268) ligands [10].

Regulatory relationships of FGFBP1

• In these cells, FGF-BP was up-regulated by treatment with epidermal growth factor (EGF), dependent on protein kinase C and p38 mitogen-activated protein kinase signaling [5].
• FGF-BP is upregulated in squamous cell carcinoma by treatment with mitogens such as EGF or TPA [11].
• The fibroblast growth factor-binding protein (FGF-BP) binds and activates fibroblast growth factors in the extracellular matrix, and can have a rate-limiting role in tumor angiogenesis [5].

Other interactions of FGFBP1

• Our results demonstrated that HBp17/FGFBP-1, like VEGF-A and FGF-2, might also promote the induction of tumor angiogenesis [8].
• Immunohistochemical expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) as an angiogenic factor in head and neck tumorigenesis [8].
• Mechanism of fibroblast growth factor-binding protein 1 repression by TGF-beta [9].
• Analysis of the downstream signaling pathways shows that Smad2/3 are crucial for efficient FGF-BP1 repression by TGF-beta [9].

References