title: Disabled-2 and Axin are concurrently colocalized and underexpressed in lung cancers.
abstract: Disabled-2 expression is reduced in many cancers, suggesting that it is a potential tumor suppressor protein. To elucidate the role of Disabled-2 in lung cancer, we examined the expression of Disabled-2, the Disabled-2-binding protein Axin, and DNA methyltransferase-1 in lung cancer tissues and corresponding normal lung tissues using immunohistochemistry and Western blots. We also determined the subcellular localization of Axin and Disabled-2 in A549 cells using confocal immunofluorescence. Disabled-2 expression was significantly reduced in lung cancers and was colocalized and coexpressed with Axin (correlation coefficient = 0.321, P < .001 for cytoplasmic expression; correlation coefficient = 0.393, P < .001 for nuclear expression). Reduced nuclear Disabled-2 expression was correlated with the differentiation (P = .048) and TNM stage (P = .048) of the tumor. The cytoplasmic expression of Axin was also correlated with differentiation (P = .042), whereas the nuclear expression of Axin was correlated with both histologic type (P = .001) and TNM stage (P < .001) of lung cancers. Expression of DNA methyltransferase-1 was negatively correlated with the cytoplasmic expression of Axin (correlation coefficient = -0.244, P = .012) but positively correlated with the histologic type (P = .004), differentiation (P = .036), TNM stage (P = .044), and lymphatic metastasis (P = .011). Expressions of Disabled-2 and Axin were concurrently reduced and correlated with the malignant phenotype of lung cancers. Enhanced expression of DNA methyltransferase-1 correlated with the reduced expression of Axin and could be a marker for lung cancer development and progression.
authors.affiliation: Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences of China Medical University, Shenyang 110001, China. xu.htao@yahoo.com.cn
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.forename: Qing-Chang
authors.initials: QC
authors.lastname: Li
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Liu
authors.forename: Di
authors.initials: D
authors.lastname: Liu
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Xie
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D012097:Repressor Proteins / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D060466:Axin Protein; D014408:Biomarkers, Tumor; C102885:DAB2 protein, human; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases