Involvement of adenosine A2B receptor in radiation-induced translocation of epidermal growth factor receptor and DNA damage response leading to radioresistance in human lung cancer cells.,Biochimica et Biophysica Acta (BBA) - General Subjects

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Involvement of adenosine A2B receptor in radiation-induced translocation of epidermal growth factor receptor and DNA damage response leading to radioresistance in human lung cancer cells.
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 2.8 ) Pub Date : 2019-10-31 , DOI: 10.1016/j.bbagen.2019.129457
Kazuki Kitabatake ₁ , Eiko Yoshida ₂ , Toshiyuki Kaji ₂ , Mitsutoshi Tsukimoto ₁

Affiliation

Background

Adenosine receptors are involved in tumor growth, progression, and response to therapy. Among them, A2B receptor is highly expressed in various tumors. Furthermore, ionizing radiation induces translocation of epidermal growth factor receptor (EGFR), which promotes DNA repair and contributes to radioresistance. We hypothesized that A2B receptor might be involved in the translocation of EGFR.

Methods

We investigated whether A2B receptor is involved in EGFR translocation and DNA damage response (γH2AX/53BP1 focus formation) of lung cancer cells by means of immunofluorescence studies. Radiosensitivity was evaluated by colony formation assay after γ-irradiation.

Results

A2B receptor was expressed at higher levels in cancer cells than in normal cells. A2B receptor antagonist treatment or A2B receptor knockdown suppressed EGFR translocation, γH2AX/53BP1 focus formation, and colony formation of lung cancer cell lines A549, calu-6 and NCI-H446, compared with a normal cell line (beas-2b). γ-Irradiation-induced phosphorylation of src and EGFR was also attenuated by suppression of A2B receptor expression.

Conclusion

Activation of A2B receptor mediates γ-radiation-induced translocation of EGFR and phosphorylation of src and EGFR, thereby promoting recovery of irradiated lung cancer cells from DNA damage.

General significance

Our results indicate that A2B receptors contribute to radiation resistance in a cancer-cell-specific manner, and may be a promising target for radiosensitizers in cancer radiotherapy.

中文翻译：

腺苷A2B受体参与辐射诱导的表皮生长因子受体的易位和DNA损伤反应，导致人肺癌细胞的抗辐射性。

背景

腺苷受体参与肿瘤的生长，进展和对治疗的反应。其中，A2B受体在各种肿瘤中高表达。此外，电离辐射诱导表皮生长因子受体（EGFR）的移位，从而促进DNA修复并有助于抗辐射。我们假设A2B受体可能与EGFR的易位有关。

方法

我们通过免疫荧光研究调查了A2B受体是否参与肺癌细胞的EGFR易位和DNA损伤反应（γH2AX/ 53BP1焦点形成）。放射线照射后，通过菌落形成试验评价放射线敏感性。

结果

与正常细胞相比，A2B受体在癌细胞中的表达水平更高。与正常细胞系（beas-2b）相比，A2B受体拮抗剂治疗或A2B受体敲低抑制了肺癌细胞系A549，calu-6和NCI-H446的EGFR易位，γH2AX/ 53BP1焦点形成和集落形成。γ射线诱导的src和EGFR磷酸化也通过抑制A2B受体表达而减弱。