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 , 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
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.
(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.