論文 - 詳細
| RRC ID | 38113 |
|---|---|
| 著者 | Kasama H, Sakamoto Y, Kasamatsu A, Okamoto A, Koyama T, Minakawa Y, Ogawara K, Yokoe H, Shiiba M, Tanzawa H, Uzawa K. |
| タイトル | Adenosine A2b receptor promotes progression of human oral cancer. |
| ジャーナル | BMC Cancer |
| Abstract |
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. |
| 巻・号 | 15 |
| ページ | 563 |
| 公開日 | 2015-7-31 |
| DOI | 10.1186/s12885-015-1577-2 |
| PII | 10.1186/s12885-015-1577-2 |
| PMID | 26228921 |
| PMC | PMC4520274 |
| MeSH | Aged Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / metabolism Carcinoma, Squamous Cell / pathology* Cell Hypoxia Cell Line, Tumor Cell Proliferation Female Gene Expression Regulation, Neoplastic Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism* Male Middle Aged Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Mouth Neoplasms / pathology* Receptor, Adenosine A2B / genetics* Receptor, Adenosine A2B / metabolism Up-Regulation |
| IF | 3.15 |
| 引用数 | 40 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) Ca9-22(RCB1976) Sa3(RCB0980) HO-1-u-1(RCB2102) SAS(RCB1974) |