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Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes.

Chen D, Stueckle TA, Luanpitpong S, Rojanasakul Y, Lu Y, Wang L - Nanoscale Res Lett (2015)

Bottom Line: A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety.More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use.Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa.

View Article: PubMed Central - PubMed

Affiliation: Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 USA.

ABSTRACT
A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

No MeSH data available.


Related in: MedlinePlus

pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells. pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells following 12 and 24 h re-exposure to dispersed SWCNT (1 to 50 μg/ml = 0.1 to 5.2 μg/cm2). β-actin was used as an internal loading control. (A) Representative blots are shown from three independent experiments. (B) pAkt/Akt ratio densitometry quantification. *indicates significant difference between the two cell types (p < 0.05). (C) Bcl-2 expression densitometry quantification. † indicates significant difference between B-SWCNT and B-Control at each time point (p < 0.05). *and # indicate significant difference of both B-Control and B-SWCNT cells, respectively, compared to its unexposed treatment group at 24 h (p < 0.05).
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Fig4: pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells. pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells following 12 and 24 h re-exposure to dispersed SWCNT (1 to 50 μg/ml = 0.1 to 5.2 μg/cm2). β-actin was used as an internal loading control. (A) Representative blots are shown from three independent experiments. (B) pAkt/Akt ratio densitometry quantification. *indicates significant difference between the two cell types (p < 0.05). (C) Bcl-2 expression densitometry quantification. † indicates significant difference between B-SWCNT and B-Control at each time point (p < 0.05). *and # indicate significant difference of both B-Control and B-SWCNT cells, respectively, compared to its unexposed treatment group at 24 h (p < 0.05).

Mentions: Akt2,PTEN, andGSK3B-mediated alteration of p53 and β-catenin function in SWCNT transformed BEAS-2B cells. Color indicates upregulation (in red) and downregulation (in green). Protein assay (Figure 4) showed no significant level changes of Akt proteins and increased phosphorylated Akt indicating that activated Akt may play a role in Gsk3β inhibition of B-catenin and MDM2-mediated p53.


Gene expression profile of human lung epithelial cells chronically exposed to single-walled carbon nanotubes.

Chen D, Stueckle TA, Luanpitpong S, Rojanasakul Y, Lu Y, Wang L - Nanoscale Res Lett (2015)

pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells. pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells following 12 and 24 h re-exposure to dispersed SWCNT (1 to 50 μg/ml = 0.1 to 5.2 μg/cm2). β-actin was used as an internal loading control. (A) Representative blots are shown from three independent experiments. (B) pAkt/Akt ratio densitometry quantification. *indicates significant difference between the two cell types (p < 0.05). (C) Bcl-2 expression densitometry quantification. † indicates significant difference between B-SWCNT and B-Control at each time point (p < 0.05). *and # indicate significant difference of both B-Control and B-SWCNT cells, respectively, compared to its unexposed treatment group at 24 h (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4314466&req=5

Fig4: pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells. pAkt, Akt, and Bcl-2 expression via SDS PAGE in B-Control and B-SWNCT transformed cells following 12 and 24 h re-exposure to dispersed SWCNT (1 to 50 μg/ml = 0.1 to 5.2 μg/cm2). β-actin was used as an internal loading control. (A) Representative blots are shown from three independent experiments. (B) pAkt/Akt ratio densitometry quantification. *indicates significant difference between the two cell types (p < 0.05). (C) Bcl-2 expression densitometry quantification. † indicates significant difference between B-SWCNT and B-Control at each time point (p < 0.05). *and # indicate significant difference of both B-Control and B-SWCNT cells, respectively, compared to its unexposed treatment group at 24 h (p < 0.05).
Mentions: Akt2,PTEN, andGSK3B-mediated alteration of p53 and β-catenin function in SWCNT transformed BEAS-2B cells. Color indicates upregulation (in red) and downregulation (in green). Protein assay (Figure 4) showed no significant level changes of Akt proteins and increased phosphorylated Akt indicating that activated Akt may play a role in Gsk3β inhibition of B-catenin and MDM2-mediated p53.

Bottom Line: A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety.More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use.Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa.

View Article: PubMed Central - PubMed

Affiliation: Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294 USA.

ABSTRACT
A rapid increase in utility of engineered nanomaterials, including carbon nanotubes (CNTs), has raised a concern over their safety. Based on recent evidence from animal studies, pulmonary exposure of CNTs may lead to nanoparticle accumulation in the deep lung without effective clearance which could interact with local lung cells for a long period of time. Physicochemical similarities of CNTs to asbestos fibers may contribute to their asbestos-like carcinogenic potential after long-term exposure, which has not been well addressed. More studies are needed to identify and predict the carcinogenic potential and mechanisms for promoting their safe use. Our previous study reported a long-term in vitro exposure model for CNT carcinogenicity and showed that 6-month sub-chronic exposure of single-walled carbon nanotubes (SWCNT) causes malignant transformation of human lung epithelial cells. In addition, the transformed cells induced tumor formation in mice and exhibited an apoptosis resistant phenotype, a key characteristic of cancer cells. Although the potential role of p53 in the transformation process was identified, the underlying mechanisms of oncogenesis remain largely undefined. Here, we further examined the gene expression profile by using genome microarrays to profile molecular mechanisms of SWCNT oncogenesis. Based on differentially expressed genes, possible mechanisms of SWCNT-associated apoptosis resistance and oncogenesis were identified, which included activation of pAkt/p53/Bcl-2 signaling axis, increased gene expression of Ras family for cell cycle control, Dsh-mediated Notch 1, and downregulation of apoptotic genes BAX and Noxa. Activated immune responses were among the major changes of biological function. Our findings shed light on potential molecular mechanisms and signaling pathways involved in SWCNT oncogenic potential.

No MeSH data available.


Related in: MedlinePlus