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Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an
Hekmat Osman Abdel-Aziz1, Yoshihiro Murai, Ichiro Takasaki
1Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
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.
Insights
Disrupting galectin-3 (gal3) significantly reduced lung tumor incidence in mice. Galectin-3 influences key signaling pathways involved in cell growth and cancer development, suggesting its role in lung carcinogenesis.
Area of Science:
- Molecular biology
- Cancer research
- Immunology
Background:
- Galectin-3 is a multifunctional protein involved in cell growth, adhesion, proliferation, angiogenesis, and apoptosis.
- These functions contribute to tumorigenesis and metastasis.
- Understanding galectin-3's role in lung carcinogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role and mechanisms of galectin-3 in lung carcinogenesis.
- To determine the effect of galectin-3 on NNK-induced lung tumors in mice.
Main Methods:
- Administered 4-(methylnitrosamino)-1-(3-pyridyle)-1-butanone (NNK) to galectin-3 wild-type (gal3+/+) and knock-out (gal3-/-) mice.
- Analyzed gene expression profiles of NNK-induced tumors using Affymetrix GeneChip arrays.
- Utilized Ingenuity Pathway Analysis for functional network and gene ontology analysis; confirmed with real-time PCR.
Main Results:
- Lung tumor incidence was significantly lower in gal3-/- mice (28.6%) compared to gal3+/+ mice (52.1%) after 32 weeks (P < 0.05).
- Galectin-3 up-regulated carcinogenesis-related genes, including B-cell receptor, ERK/MAPK, and PPAR signaling pathways.
- In lung carcinogenesis, galectin-3 influenced gene expression related to cellular growth (Wnt/beta-catenin) and immunological disease (EGF, PDGF signaling).
Conclusions:
- Disruption of galectin-3 attenuates lung carcinogenesis.
- Galectin-3 plays a regulatory role in B-cell receptor, ERK/MAPK, and PPAR signaling pathways, impacting lung cancer development.