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Adenosine A2b receptor promotes progression of human oral cancer

BACKGROUND: Adenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malign...

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Autores principales: Kasama, Hiroki, Sakamoto, Yosuke, Kasamatsu, Atsushi, Okamoto, Atsushi, Koyama, Tomoyoshi, Minakawa, Yasuyuki, Ogawara, Katsunori, Yokoe, Hidetaka, Shiiba, Masashi, Tanzawa, Hideki, Uzawa, Katsuhiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520274/
https://www.ncbi.nlm.nih.gov/pubmed/26228921
http://dx.doi.org/10.1186/s12885-015-1577-2
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author Kasama, Hiroki
Sakamoto, Yosuke
Kasamatsu, Atsushi
Okamoto, Atsushi
Koyama, Tomoyoshi
Minakawa, Yasuyuki
Ogawara, Katsunori
Yokoe, Hidetaka
Shiiba, Masashi
Tanzawa, Hideki
Uzawa, Katsuhiro
author_facet Kasama, Hiroki
Sakamoto, Yosuke
Kasamatsu, Atsushi
Okamoto, Atsushi
Koyama, Tomoyoshi
Minakawa, Yasuyuki
Ogawara, Katsunori
Yokoe, Hidetaka
Shiiba, Masashi
Tanzawa, Hideki
Uzawa, Katsuhiro
author_sort Kasama, Hiroki
collection PubMed
description BACKGROUND: Adenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of ADORA2B in OSCC. METHODS: The ADORA2B expression levels in nine OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using an ADORA2B knockdown model, we assessed cellular proliferation and expression of hypoxia-inducible factor1α (HIF-1α). We examined the adenosine receptor expression profile under both normoxic and hypoxic conditions in the OSCC-derived cells. In addition to in vitro data, the clinical correlation between the ADORA2B expression levels in primary OSCCs (n = 100 patients) and the clinicopathological status by immunohistochemistry (IHC) also was evaluated. RESULTS: ADORA2B mRNA and protein were up-regulated significantly (p < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. Suppression of ADORA2B expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells. HIF-1α also was down-regulated in ADORA2B knockdown OSCC cells. During hypoxia, ADORA2B expression was induced significantly (p < 0.05) in the mRNA and protein after 24 hours of incubation in OSCC-derived cells. IHC showed that ADORA2B expression in primary OSCCs was significantly (p < 0.05) greater than in the normal oral counterparts and that ADORA2B-positive OSCCs were correlated closely (p < 0.05) with tumoral size. CONCLUSION: Our results suggested that ADORA2B controls cellular proliferation via HIF-1α activation, indicating that ADORA2B may be a key regulator of tumoral progression in OSCCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1577-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-45202742015-07-31 Adenosine A2b receptor promotes progression of human oral cancer Kasama, Hiroki Sakamoto, Yosuke Kasamatsu, Atsushi Okamoto, Atsushi Koyama, Tomoyoshi Minakawa, Yasuyuki Ogawara, Katsunori Yokoe, Hidetaka Shiiba, Masashi Tanzawa, Hideki Uzawa, Katsuhiro BMC Cancer Research Article BACKGROUND: Adenosine A2b receptor (ADORA2B) encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. Little is known about the relevance of ADORA2B to human malignancy including oral squamous cell carcinoma (OSCC). We aimed to characterize the expression state and function of ADORA2B in OSCC. METHODS: The ADORA2B expression levels in nine OSCC-derived cells were analyzed by quantitative reverse transcriptase-polymerase chain reaction and immunoblotting analyses. Using an ADORA2B knockdown model, we assessed cellular proliferation and expression of hypoxia-inducible factor1α (HIF-1α). We examined the adenosine receptor expression profile under both normoxic and hypoxic conditions in the OSCC-derived cells. In addition to in vitro data, the clinical correlation between the ADORA2B expression levels in primary OSCCs (n = 100 patients) and the clinicopathological status by immunohistochemistry (IHC) also was evaluated. RESULTS: ADORA2B mRNA and protein were up-regulated significantly (p < 0.05) in seven OSCC-derived cells compared with human normal oral keratinocytes. Suppression of ADORA2B expression with shRNA significantly (p < 0.05) inhibited cellular proliferation compared with the control cells. HIF-1α also was down-regulated in ADORA2B knockdown OSCC cells. During hypoxia, ADORA2B expression was induced significantly (p < 0.05) in the mRNA and protein after 24 hours of incubation in OSCC-derived cells. IHC showed that ADORA2B expression in primary OSCCs was significantly (p < 0.05) greater than in the normal oral counterparts and that ADORA2B-positive OSCCs were correlated closely (p < 0.05) with tumoral size. CONCLUSION: Our results suggested that ADORA2B controls cellular proliferation via HIF-1α activation, indicating that ADORA2B may be a key regulator of tumoral progression in OSCCs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-1577-2) contains supplementary material, which is available to authorized users. BioMed Central 2015-07-31 /pmc/articles/PMC4520274/ /pubmed/26228921 http://dx.doi.org/10.1186/s12885-015-1577-2 Text en © Kasama et al. 2015 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Kasama, Hiroki
Sakamoto, Yosuke
Kasamatsu, Atsushi
Okamoto, Atsushi
Koyama, Tomoyoshi
Minakawa, Yasuyuki
Ogawara, Katsunori
Yokoe, Hidetaka
Shiiba, Masashi
Tanzawa, Hideki
Uzawa, Katsuhiro
Adenosine A2b receptor promotes progression of human oral cancer
title Adenosine A2b receptor promotes progression of human oral cancer
title_full Adenosine A2b receptor promotes progression of human oral cancer
title_fullStr Adenosine A2b receptor promotes progression of human oral cancer
title_full_unstemmed Adenosine A2b receptor promotes progression of human oral cancer
title_short Adenosine A2b receptor promotes progression of human oral cancer
title_sort adenosine a2b receptor promotes progression of human oral cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4520274/
https://www.ncbi.nlm.nih.gov/pubmed/26228921
http://dx.doi.org/10.1186/s12885-015-1577-2
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