Abbreviations: Areg:
amphiregulin; ECs: epithelial cells; IL: interleukin; ILC2: type 2 innate lymphoid cell; MCs: mast cells; PGI2: prostaglandin I2; Th9: T-helper type 9; Treg: T regulatory cells.
The neurophilic factors essentially AGRP (agouti-related protein), BNDF (brain-derived neurotrophic factor), CNTF (human ciliary neurotrophic factor), AREG (schwannoma-derived growth factor,
Amphiregulin) is a growth factor as well as a mitogen for astrocytes, Schwann cells, and fibroblasts [18], b-NGF (basic nerve growth factor), NT-3 (neurotrophin-3), NT-4 (neurotrophin-3), activin A, and prolactin (Table 1(d)).
Expression of epiregulin and
amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab.
Accession numbers of ErbB2 ligands Protein Accession number EGF NP_001954 HRG-[alpha] NP_039258 HRG-[beta] NP_039250 TGF-[alpha] NP_003227 Betacellulin NP_001720
Amphiregulin NP_001648
Recombinant human
amphiregulin was purchased from R&D Systems (Minneapolis, USA), aliquoted in sterile PBS containing 0.1% BSA, and used in final concentrations of 0.5 or 0.05 [less than or equal to]g/ml.
The N-terminal part of the fusion protein is critical for transforming activity, and the fusion protein activates epidermal growth factor receptor signaling in an autocrine manner and activates transcription of cAMP/cAMP response element-binding protein target genes including phosphoenolpyruvate carboxykinase 1;
amphiregulin; MMP10; interleukin 6; nuclear receptor subfamily 4, group A, member 2; and nuclear receptor subfamily 4, group A, member 3.
ErbB members exist as monomers that dimerize in response to receptor-specific ligands, such as
amphiregulin and epidermal growth factor (EGF), for EGFR.
Out of these eight genes,
amphiregulin (AREG), fibulin 1 (FBLN1), and claudin 6 (CLDN6) were the most differentially expressed.
Fourteen differentially expressed genes (AREG (
Amphiregulin), ATRN (Attractin), CD59 (CD59 molecule), CLU (Clusterin), CST3 (Cystatin C), DPEP1 (Dipeptidase), EPHX1 (Epoxide hydrolase), LEAP2 (Liver expressed antimicrobial peptide 2), LOC396871 (Arginine rich antibacterial peptides), MS4A2 (Membrane-spanning 4-domains), PIAP (Putative inhibitor of apoptosis), RETN (Resistin), UBP (Ubiquitin-specific protease), FBP (Folate binding protein) dentified in the array experiment were selected and analyzed by RT-qPCR.
There is evidence that the EGFR ligands epiregulin and
amphiregulin are important for prediction of response to cetuximab.
(80) On the other hand, ADAMTS-1 also facilitates cell invasion by cleaving heparin-binding epithelial growth factor-like growth factor and
amphiregulin. (81,82) Interestingly, in our data from the protease arrays of the UMSCC1 cells, the secreted levels of ADAMTS-1 was identified as being significantly diminished in conditioned cell culture medium from UMSCC1 cells with increased miR-375 expression compared to its control line.
Amphiregulin (AREG) is a member of the epidermal growth factor family that combines with the epidermal growth factor receptor (EGFR) and activates the downstream of signalling pathway.