title: Abnormal hypermethylation and clinicopathological significance of Axin gene in lung cancer.
abstract: Axin is an important negative regulator of Wnt pathway. We have reported that reduced expression of Axin could be detected in lung cancer tissues, but the mechanism is not clear. By analyzing the genomic sequence, we note that Axin gene promoter is rich in CpGs. Little is known about the methylation status of Axin gene in lung cancer. So, nested MSP and RT-PCR were used to study the methylation status and mRNA expression of Axin gene in lung cancer tissues and cell lines. The results showed that hypermethylated Axin gene promoter and reduced mRNA expression level of Axin could be detected in lung cancer tissues but not in their paired autologous normal lung tissues (P < 0.01). The hypermethylated Axin gene promoter significantly correlated with the degree of differentiation (P = 0.03), lymph node metastasis (P = 0.048) and TNM classifications (P = 0.032). Demethylation reagent 5-aza-2-deoxycytidine significantly up-regulate Axin expression in BE1 cells (with hypermethylated Axin gene promoter) but not in H460 cells (with unmethylated Axin gene promoter). MTT (3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and transwell matrigel invasion assay showed that 5-aza-2-deoxycytidine treatment inhibited cell growth and invasion more significantly in BE1 cells than that in H460 cells. Our data indicate that hypermethylated Axin gene significantly correlates with the progression of lung cancer and might serve as a new target of clinical therapy for lung cancer patients in future.
authors.affiliation: Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, Liaoning, China.
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Qing-Chang
authors.initials: QC
authors.lastname: Li
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Jiang
authors.forename: Xiu-Peng
authors.initials: XP
authors.lastname: Zhang
authors.forename: Huan-Yu
authors.initials: HY
authors.lastname: Zhao
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060466:Axin Protein / Q000235:genetics*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine