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ARNT2 Regulates Tumoral Growth in Oral Squamous Cell Carcinoma.

Kimura Y, Kasamatsu A, Nakashima D, Yamatoji M, Minakawa Y, Koike K, Fushimi K, Higo M, Endo-Sakamoto Y, Shiiba M, Tanzawa H, Uzawa K - J Cancer (2016)

Bottom Line: ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts.In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size.Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;

ABSTRACT
Aryl hydrocarbon receptor nuclear translocator (ARNT) 2 is a transcriptional factor related to adaptive responses against cellular stress from a xenobiotic substance. Recent evidence indicates ARNT is involved in carcinogenesis and cancer progression; however, little is known about the relevance of ARNT2 in the behavior of oral squamous cell carcinoma (OSCC). In the current study, we evaluated the ARNT2 mRNA and protein expression levels in OSCC in vitro and in vivo and the clinical relationship between ARNT2 expression levels in primary OSCCs and their clinicopathologic status by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry. Using ARNT2 overexpression models, we performed functional analyses to investigate the critical roles of ARNT2 in OSCC. ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts. In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size. Since von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase, a negative regulator of hypoxia-inducible factor (HIF1)-α, is a downstream molecule of ARNT2, we speculated that HIF1-α and its downstream molecules would have key functions in cellular growth. Consistent with our hypothesis, overexpressed ARNT2 cells showed down-regulation of HIF1-α, which causes hypofunctioning of glucose transporter 1, leading to decreased cellular growth. Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs. Therefore, ARNT2 may be a potential therapeutic target against progression of OSCCs.

No MeSH data available.


Related in: MedlinePlus

Evaluation of ARNT2 expression in OSCC-derived cell lines. (A) Quantification of ARNT2 mRNA expression in OSCC-derived cell lines by qRT-PCR analysis. Significant (*P < 0.05, Mann-Whitney U-test) down-regulation of ARNT2 mRNA is seen in nine OSCC-derived cell lines compared with HNOKs. Data are expressed as the means ± standard errors of the mean of triplicate results. (B) Immunoblot analysis of ARNT2 protein in OSCC-derived cell lines and HNOKs. ARNT2 protein expression is down-regulated in OSCC-derived cell lines compared with that in HNOKs. Densitometric ARNT2 protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of HNOKs.
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Figure 1: Evaluation of ARNT2 expression in OSCC-derived cell lines. (A) Quantification of ARNT2 mRNA expression in OSCC-derived cell lines by qRT-PCR analysis. Significant (*P < 0.05, Mann-Whitney U-test) down-regulation of ARNT2 mRNA is seen in nine OSCC-derived cell lines compared with HNOKs. Data are expressed as the means ± standard errors of the mean of triplicate results. (B) Immunoblot analysis of ARNT2 protein in OSCC-derived cell lines and HNOKs. ARNT2 protein expression is down-regulated in OSCC-derived cell lines compared with that in HNOKs. Densitometric ARNT2 protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of HNOKs.

Mentions: To investigate the expression status of ARNT2, we performed qRT-PCR and immunoblot analyses using nine OSCC-derived cell lines (HSC-2, HSC-3, HSC-4, KOSC-2, Ho-1-u-1, Ho-1-N-1, Sa3, Ca9-22, and SAS) and HNOKs. ARNT2 mRNA was down-regulated significantly (P < 0.05) in all OSCC-derived cell lines compared with the HNOKs (Fig. 1A). Fig. 1B shows representative results of immunoblot analysis. The ARNT2 protein expression decreased significantly (P < 0.05) in all OSCC-derived cell lines compared with the HNOKs.


ARNT2 Regulates Tumoral Growth in Oral Squamous Cell Carcinoma.

Kimura Y, Kasamatsu A, Nakashima D, Yamatoji M, Minakawa Y, Koike K, Fushimi K, Higo M, Endo-Sakamoto Y, Shiiba M, Tanzawa H, Uzawa K - J Cancer (2016)

Evaluation of ARNT2 expression in OSCC-derived cell lines. (A) Quantification of ARNT2 mRNA expression in OSCC-derived cell lines by qRT-PCR analysis. Significant (*P < 0.05, Mann-Whitney U-test) down-regulation of ARNT2 mRNA is seen in nine OSCC-derived cell lines compared with HNOKs. Data are expressed as the means ± standard errors of the mean of triplicate results. (B) Immunoblot analysis of ARNT2 protein in OSCC-derived cell lines and HNOKs. ARNT2 protein expression is down-regulated in OSCC-derived cell lines compared with that in HNOKs. Densitometric ARNT2 protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of HNOKs.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4829557&req=5

Figure 1: Evaluation of ARNT2 expression in OSCC-derived cell lines. (A) Quantification of ARNT2 mRNA expression in OSCC-derived cell lines by qRT-PCR analysis. Significant (*P < 0.05, Mann-Whitney U-test) down-regulation of ARNT2 mRNA is seen in nine OSCC-derived cell lines compared with HNOKs. Data are expressed as the means ± standard errors of the mean of triplicate results. (B) Immunoblot analysis of ARNT2 protein in OSCC-derived cell lines and HNOKs. ARNT2 protein expression is down-regulated in OSCC-derived cell lines compared with that in HNOKs. Densitometric ARNT2 protein data are normalized to GAPDH protein levels. The values are expressed as a percentage of HNOKs.
Mentions: To investigate the expression status of ARNT2, we performed qRT-PCR and immunoblot analyses using nine OSCC-derived cell lines (HSC-2, HSC-3, HSC-4, KOSC-2, Ho-1-u-1, Ho-1-N-1, Sa3, Ca9-22, and SAS) and HNOKs. ARNT2 mRNA was down-regulated significantly (P < 0.05) in all OSCC-derived cell lines compared with the HNOKs (Fig. 1A). Fig. 1B shows representative results of immunoblot analysis. The ARNT2 protein expression decreased significantly (P < 0.05) in all OSCC-derived cell lines compared with the HNOKs.

Bottom Line: ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts.In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size.Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Oral Science, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan;

ABSTRACT
Aryl hydrocarbon receptor nuclear translocator (ARNT) 2 is a transcriptional factor related to adaptive responses against cellular stress from a xenobiotic substance. Recent evidence indicates ARNT is involved in carcinogenesis and cancer progression; however, little is known about the relevance of ARNT2 in the behavior of oral squamous cell carcinoma (OSCC). In the current study, we evaluated the ARNT2 mRNA and protein expression levels in OSCC in vitro and in vivo and the clinical relationship between ARNT2 expression levels in primary OSCCs and their clinicopathologic status by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting, and immunohistochemistry. Using ARNT2 overexpression models, we performed functional analyses to investigate the critical roles of ARNT2 in OSCC. ARNT2 mRNA and protein were down-regulated significantly (P < 0.05 for both comparisons) in nine OSCC-derived cells and primary OSCC (n=100 patients) compared with normal counterparts. In addition to the data from exogenous experiments that ARNT2-overexpressed cells showed decreased cellular proliferation, ARNT2-positive OSCC cases were correlated significantly (P < 0.05) with tumoral size. Since von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase, a negative regulator of hypoxia-inducible factor (HIF1)-α, is a downstream molecule of ARNT2, we speculated that HIF1-α and its downstream molecules would have key functions in cellular growth. Consistent with our hypothesis, overexpressed ARNT2 cells showed down-regulation of HIF1-α, which causes hypofunctioning of glucose transporter 1, leading to decreased cellular growth. Our results proposed for the first time that the ARNT2 level is an indicator of cellular proliferation in OSCCs. Therefore, ARNT2 may be a potential therapeutic target against progression of OSCCs.

No MeSH data available.


Related in: MedlinePlus