title: AKT signaling pathway activated by HIN-1 methylation in non-small cell lung cancer.
abstract: The purpose of this study is to determine the epigenetic changes and function of High in Normal-1 (HIN-1) in non-small cell lung cancer (NSCLC). HIN-1 expression was examined by semiquantitative RT-PCR before and after 5-aza-2'-deoxycytidine (5-aza) treatment in NSCLC cell lines. Promoter methylation status of HIN-1 was tested by methylation-specific PCR (MSP). Effect of forced expression of HIN-1 on different key molecules of AKT signaling pathway was tested by Western Blot analysis in H157 and H23 cell lines. Promoter methylations are inversely correlated with expression of HIN-1 in eight (H23, H157, 95D, H1299, H358, H1752, H460, A549) of ten NSCLC cell lines and re-expression was observed by 5-aza treatment. We then tested promoter methylation of HIN-1 in primary NSCLC tissues. Methylation was detected in 73 out of 152 (48%) NSCLC cases. Forced expression of HIN-1 in NSCLC cell lines inhibited colony formation and induce apoptosis. Furthermore, overexpression of HIN-1 reduces the expression of phosphorated-AKT (p-AKT), c-myc, Bcl-2 and cyclinD1 while Bax was increased. Our data suggest that HIN-1 is a potential tumor suppressor gene in NSCLC, silenced by promoter hypermethylation and negatively regulate AKT signaling pathway.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853, China.
authors.forename: Yuanzi
authors.initials: Y
authors.lastname: Yu
authors.forename: Dongtao
authors.initials: D
authors.lastname: Yin
authors.forename: Mohammad O
authors.initials: MO
authors.lastname: Hoque
authors.forename: Baoping
authors.initials: B
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Jia
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yang
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D000368:Aged; D001374:Azacitidine / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D016207:Cytokines; C434732:SCGB3A1 protein, human; D025521:Tumor Suppressor Proteins; D051057:Proto-Oncogene Proteins c-akt; D001374:Azacitidine
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