Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray study
Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray study
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DOI：
10.1007/s00432-007-0345-3
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发表时间：
2008-07-01
影响因子：
3.6
通讯作者：
Takano, Yasuo
中科院分区：
文献类型：
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作者：
Abdel-Aziz, Hekmat Osman;Murai, Yoshihiro;Takano, Yasuo
目的Galectin-3是一种β-半乳糖苷结合的动物凝集素，是一种多功能蛋白，调节细胞生长、细胞黏附、细胞增殖、血管生成和细胞凋亡，进而促进肿瘤的发生和转移。方法通过对Galectin-3野生型(Galectin-3+/+)和Galectin-3基因敲除型(Gal3-/-)CD1小鼠体内注射化学致癌剂4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone，利用Affymetrix基因芯片小鼠表达谱430A阵列检测NNK诱发肿瘤的22,690个小鼠基因的表达情况，并通过独创性路径分析进行功能网络和基因本体论分析。结果与Gal3+/+小鼠相比，Gal3-/-小鼠32周后肺癌发生率显著降低(28.6%比52.1%，P<；0.05)。通路分析表明，Galectin-3在正常状态下上调了致癌相关基因(如B细胞受体、ERK/MAPK和PPAR信号)的表达，在肺癌和NNK诱导的肺癌发生过程中分别上调了与细胞生长(如Wnt/β-catenin信号)或免疫疾病(如EGF和PDGF信号)相关的基因表达。结论Galectin-3可能通过调节B细胞受体、ERK/MAPK和PPAR信号通路而减轻肺癌的发生。
Purpose Galectin-3, a beta-galactoside-binding animal lectin is a multifunctional protein, which regulates cell growth, cell adhesion, cell proliferation, angiogenesis, and apoptosis, and in turn contributes to tumorigenesis and metastasis. The aim of this study was to clarify the role or related mechanisms of galectin-3 in lung carcinogenesis.Methods We administrated 4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone (NNK), a powerful chemical carcinogen into galectin-3 wild-type (gal3+/+) and galectin-3 knock-out (gal3-/-) CD1 mice by intraperitoneal injection, examined the expression status of 22,690 mouse genes of the NNK-induced tumors using Affymetrix GeneChip mouse expression 430 A arrays, and then analyzed functional network and gene ontology by Ingenuity Pathway Analysis. Real-time PCR was also employed to partially confirm the genechip data.Results Compared with the gal3+/+ mice, the incidence of lung tumors was significantly low in gal3-/- mice after 32 weeks (28.6 vs 52.1%, P < 0.05). Pathway analysis indicated that galectin-3 up-regulated carcinogenesis-related genes (e.g. B-cell receptor, ERK/MAPK, and PPAR signalings) in normal condition, and lung cancer and NNK-induced gene expression associated with cellular growth (e.g. Wnt/beta-catenin signaling) or immunological disease (e.g. EGF and PDGF signalings) in lung carcinogenesis with or without the galectin-3 control, respectively.Conclusion Disrupted galectin-3 may attenuate the lung carcinogenesis due to its regulatory role in the B-cell receptor, ERK/MAPK, and PPAR signal pathways.