Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis

An oligonucleotide microarray study

Hekmat Osman Abdel-Aziz, Yoshihiro Murai, Ichiro Takasaki, Yoshiaki Tabuchi, Hua Chuan Zheng, Kazuhiro Nomoto, Hiroyuki Takahashi, Koichi Tsuneyama, Ichiro Kato, Daniel K. Hsu, Fu-Tong Liu, Koichi Hiraga, Yasuo Takano

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Purpose: Galectin-3, a β-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/β-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.

Original languageEnglish (US)
Pages (from-to)777-788
Number of pages12
JournalJournal of Cancer Research and Clinical Oncology
Volume134
Issue number7
DOIs
StatePublished - Jul 2008

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Galectin 3
Oligonucleotide Array Sequence Analysis
Carcinogenesis
Lung
Genes
Peroxisome Proliferator-Activated Receptors
B-Lymphocytes
Butanones
Galactosides
Catenins
Gene Ontology
Immune System Diseases
Growth
Intraperitoneal Injections
Epidermal Growth Factor
Lectins
Cell Adhesion
Carcinogens
Real-Time Polymerase Chain Reaction
Signal Transduction

Keywords

  • Galectin-3
  • IPA
  • Lung tumor
  • NNK
  • Oligonucleotide microarrays

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis : An oligonucleotide microarray study. / Abdel-Aziz, Hekmat Osman; Murai, Yoshihiro; Takasaki, Ichiro; Tabuchi, Yoshiaki; Zheng, Hua Chuan; Nomoto, Kazuhiro; Takahashi, Hiroyuki; Tsuneyama, Koichi; Kato, Ichiro; Hsu, Daniel K.; Liu, Fu-Tong; Hiraga, Koichi; Takano, Yasuo.

In: Journal of Cancer Research and Clinical Oncology, Vol. 134, No. 7, 07.2008, p. 777-788.

Research output: Contribution to journalArticle

Abdel-Aziz, HO, Murai, Y, Takasaki, I, Tabuchi, Y, Zheng, HC, Nomoto, K, Takahashi, H, Tsuneyama, K, Kato, I, Hsu, DK, Liu, F-T, Hiraga, K & Takano, Y 2008, 'Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: An oligonucleotide microarray study', Journal of Cancer Research and Clinical Oncology, vol. 134, no. 7, pp. 777-788. https://doi.org/10.1007/s00432-007-0345-3
Abdel-Aziz, Hekmat Osman ; Murai, Yoshihiro ; Takasaki, Ichiro ; Tabuchi, Yoshiaki ; Zheng, Hua Chuan ; Nomoto, Kazuhiro ; Takahashi, Hiroyuki ; Tsuneyama, Koichi ; Kato, Ichiro ; Hsu, Daniel K. ; Liu, Fu-Tong ; Hiraga, Koichi ; Takano, Yasuo. / Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis : An oligonucleotide microarray study. In: Journal of Cancer Research and Clinical Oncology. 2008 ; Vol. 134, No. 7. pp. 777-788.
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abstract = "Purpose: Galectin-3, a β-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/β-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.",
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T2 - An oligonucleotide microarray study

AU - Abdel-Aziz, Hekmat Osman

AU - Murai, Yoshihiro

AU - Takasaki, Ichiro

AU - Tabuchi, Yoshiaki

AU - Zheng, Hua Chuan

AU - Nomoto, Kazuhiro

AU - Takahashi, Hiroyuki

AU - Tsuneyama, Koichi

AU - Kato, Ichiro

AU - Hsu, Daniel K.

AU - Liu, Fu-Tong

AU - Hiraga, Koichi

AU - Takano, Yasuo

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N2 - Purpose: Galectin-3, a β-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/β-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.

AB - Purpose: Galectin-3, a β-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/β-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.

KW - Galectin-3

KW - IPA

KW - Lung tumor

KW - NNK

KW - Oligonucleotide microarrays

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