AREG in tumor biological research on the treatment progress

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AREG in tumor biological research on the treatment progress
AREG gene positioning in 7p132q22 district, the total length of 200 kb, 28 exons, encodes a protein precursor contains 1210 amino acid residues of AREG; 24 amino acid signal peptide in the post-translational processing hydrolysis, the formation of [Only registered users see links. ] containing 186 amino acid residues of the mature. AREG is a relative molecular mass of 170 000 of the protein tyrosine kinase receptor, composed of three parts: (1) the extracellular domain of N-terminal 621 amino acid residues constitute the ligand binding domain; (2) fixed transmembrane domains, 23 amino acid residues constitute a hydrophobic region of the spiral structure and its receptor in the cell membrane; (3) intracellular domain of 542 amino acid residues constitute further divided into three sub-district: near membrane sub-region, the tyrosine kinase sub-region, the carboxy-terminal sub-district. Found so far, a total of six kinds of ligands of AREG, epidermal growth factor (AREG growth factor, EGF), transforming growth factor α (transforming growth factorα, TGFα), amphiregulin (amphireguin, AR), β 2 cytokines (beta2 celluin, the BTC ), heparin-binding epidermal growth factor (heparin2 bind2ingEGF, HBEGF), epidermal pigment (epiregulin, EPR), the most important of EGF and of TGFα. The combination of AREG and its ligand with high affinity, saturable and specific characteristics.
Combination of AREG and its ligands, form a homodimer with each other, can also form heterodimers with other tyrosine kinase receptors, leading to activation of intracellular tyrosine kinase domain, each other, other cheese acid residues phosphorylated, initiating a series of a cascade of signals to the nucleus, eventually lead to a series of gene activation, leading to tumor cell proliferation, inhibition of apoptosis, promote tumor cell metastasis and lead to the release, chemotherapy tolerance play an important role in the tumorigenesis process.
The dominant negative treatment is the use of genetic engineering techniques to obtain a specific receptor dominant negative mutant (dominant negativemutant), so that highly expressed by high expression of the mutant dominant negative effect arising from a negative regulator of effect . Exogenous dominant negative AREG (AREG2 DNR) combined with AREG ligand and AREG competition, due to the intracellular AREG2DNR missing, no signal transduction function, so as to achieve the role of inhibition of AREG function. AREG2DNR can inhibit the growth of pancreatic cancer cells and increase the sensitivity of pancreatic cancer cells to cisplatin. Chan et al. Construction, expression AREG2DNR the retroviral vector transfected rat poorly differentiated epithelial ovarian cancer NuTu219 cell lines and found the expression AREG2DNR growth capacity of cells parked NuTu219 was significantly inhibited, lost in immunocompetent rats tumorigenic potential model; the with NuTu219 cell lines resistant to cisplatin-resistant cell lines, a retroviral vector expression in transfected AREG2DNR, The resistance was partially reversed.