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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

Cellular proliferation of ARNT2 overexpressed cells. (A) To determine the effect of ARNT2 overexpression on cellular proliferation, oeARNT2 and Mock cells are seeded in six-well plates at a density of 1 × 104 viable cells per well. Both transfectants are cultured for 168 hours and counted every 24 hours. The oeARNT2 cells have significantly (P < 0.05) decreased cellular growth compared with the Mock cells. (B) Images are obtained after 12 and 120 hours using a Leica LCD microscope (original magnification, x200) and are representative of three independent experiments. The results are expressed as the means ± standard errors of the mean of values from three assays. h, hours.
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Figure 4: Cellular proliferation of ARNT2 overexpressed cells. (A) To determine the effect of ARNT2 overexpression on cellular proliferation, oeARNT2 and Mock cells are seeded in six-well plates at a density of 1 × 104 viable cells per well. Both transfectants are cultured for 168 hours and counted every 24 hours. The oeARNT2 cells have significantly (P < 0.05) decreased cellular growth compared with the Mock cells. (B) Images are obtained after 12 and 120 hours using a Leica LCD microscope (original magnification, x200) and are representative of three independent experiments. The results are expressed as the means ± standard errors of the mean of values from three assays. h, hours.

Mentions: To evaluate the effect of ARNT2 overexpression on cellular growth, we performed a cellular proliferation assay. We found a significant (P < 0.05) decrease in cellular growth in the oeARNT2 cells compared with the Mock cells (Fig. 4A). Images were obtained after 12 and 120 hours using a Leica LCD microscope (Leica Microsystems, Wetzlar, Germany) (original magnification, x200) (Fig. 4B).


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)

Cellular proliferation of ARNT2 overexpressed cells. (A) To determine the effect of ARNT2 overexpression on cellular proliferation, oeARNT2 and Mock cells are seeded in six-well plates at a density of 1 × 104 viable cells per well. Both transfectants are cultured for 168 hours and counted every 24 hours. The oeARNT2 cells have significantly (P < 0.05) decreased cellular growth compared with the Mock cells. (B) Images are obtained after 12 and 120 hours using a Leica LCD microscope (original magnification, x200) and are representative of three independent experiments. The results are expressed as the means ± standard errors of the mean of values from three assays. h, hours.
© Copyright Policy
Related In: Results  -  Collection

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Figure 4: Cellular proliferation of ARNT2 overexpressed cells. (A) To determine the effect of ARNT2 overexpression on cellular proliferation, oeARNT2 and Mock cells are seeded in six-well plates at a density of 1 × 104 viable cells per well. Both transfectants are cultured for 168 hours and counted every 24 hours. The oeARNT2 cells have significantly (P < 0.05) decreased cellular growth compared with the Mock cells. (B) Images are obtained after 12 and 120 hours using a Leica LCD microscope (original magnification, x200) and are representative of three independent experiments. The results are expressed as the means ± standard errors of the mean of values from three assays. h, hours.
Mentions: To evaluate the effect of ARNT2 overexpression on cellular growth, we performed a cellular proliferation assay. We found a significant (P < 0.05) decrease in cellular growth in the oeARNT2 cells compared with the Mock cells (Fig. 4A). Images were obtained after 12 and 120 hours using a Leica LCD microscope (Leica Microsystems, Wetzlar, Germany) (original magnification, x200) (Fig. 4B).

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