title: Association of single nucleotide polymorphisms of β2-adrenergic receptor gene with clinicopathological features of pancreatic carcinoma.
abstract: β2-Adrenoceptor agonists induce pancreatic cancer occurrence and progression through β2-AR. Polymorphisms in β2-AR gene lead to modified sensitivity to agonists and variable tumorigenic potential. In this study, pancreatic carcinoma and non-neoplastic pancreatic tissues were genotyped at codons 16 and 27 by PCR-restriction fragment length polymorphism and DNA sequencing. Expressions of β2-AR, EGFR, VEGF and MMP-2 were detected by immunohistochemistry. The frequencies of genotypes and alleles at codon 16 between pancreatic carcinoma and non-neoplastic pancreatic tissues showed no difference. The genotype frequencies were associated with TNM grade, lymph node metastasis, and one-year survival rate. The allele G at codon 16 frequently appeared in tumors with high TNM grade, lymph node metastasis, poor prognosis, high expression levels of β2-AR, EGFR, VEGF and MMP-2. The genotype and allele frequencies of codon 27 were not associated with clinicopathological features and down-stream protein expressions. Collectively, SNPs of β2-AR gene at codon 16 were associated with the biological behavior of pancreatic carcinoma. The allele G at codon 16 could facilitate the progression and metastasis of pancreatic carcinoma through elevating vascularization and activating the EGFR pathway. SNPs at codon 16 of β2-AR are new useful biomarkers for predicting biological behavior and survival of pancreatic carcinoma and might be used as a new gene therapeutic target.
authors: Department of Pathology, The Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
authors: Yu
authors: Y
authors: Wenjuan
authors: Li
authors: L
authors: Yujun
authors: Yu
authors: Y
authors: Ceng
mesh_terms: D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis / Q000235:genetics*; D042442:Vascular Endothelial Growth Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018343:Receptors, Adrenergic, beta-2; D042442:Vascular Endothelial Growth Factors; D066246:ErbB Receptors; D020778:Matrix Metalloproteinase 2