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 language | English (US) |
|---|---|
| Pages (from-to) | 777-788 |
| Number of pages | 12 |
| Journal | Journal of Cancer Research and Clinical Oncology |
| Volume | 134 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis
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
PY - 2008/7
Y1 - 2008/7
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
UR - http://www.scopus.com/inward/record.url?scp=43449131256&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=43449131256&partnerID=8YFLogxK
U2 - 10.1007/s00432-007-0345-3
DO - 10.1007/s00432-007-0345-3
M3 - Article
VL - 134
SP - 777
EP - 788
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 7
ER -