| 乳腺癌中神经激肽受体的表达及受体拮抗剂的作用研究* |
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| 引用本文： | 周云丽, 王萌, 仝颖娜, 刘晓彬, 董冬, 邵洁. 乳腺癌中神经激肽受体的表达及受体拮抗剂的作用研究*[J]. 中国肿瘤临床, 2015, 42(24): 1167-1173. DOI: 10.3969/j.issn.1000-8179.2015.24.112 |
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| 作者姓名： | 周云丽 王萌 仝颖娜 刘晓彬 董冬 邵洁 |
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| 作者单位： | 作者单位:天津医科大学肿瘤医院检验科,国家肿瘤临床医学研究中心,乳腺癌防治教育部重点实验室(天津市300060) |
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| 摘 要： | 目的：研究乳腺癌中全长型、截短型神经激肽1 受体（neurokinin 1 receptor，NK1R）和神经激肽2 受体（neurokinin 2 receptor，NK2R）的表达，及受体拮抗剂对乳腺癌细胞生长的影响。方法：采用免疫组织化学法检测天津医科大学肿瘤医院51例乳腺癌及其癌旁正常组织、30例乳腺良性病变组织总NK1R（包括NK1R-FL和NK1R-Tr）和NK2R 表达，采用实时定量PCR 和免疫印迹技术检测乳腺细胞系中NK1R-FL、NK1R-Tr和NK2R 表达，建立NK1R-FL和NK1R-Tr过表达的乳腺细胞系, 在NK1R 和NK2R 拮抗剂作用下测定细胞增殖和软琼脂集落形成能力。结果：乳腺癌及癌旁正常组织、乳腺良性病变组织中均总NK1R 过表达，乳腺癌组织中 NK1R-FL、NK2R 表达相比癌旁正常组织显著降低，并与乳腺癌分型、组织学分级、淋巴结转移及 Ki-67、HER-2、ER和PR表达相关。HBL-100 细胞中NK1R-FL和NK2R 过表达、NK1R-Tr低表达，MDA-MB-231、T-47D 和MCF-7 细胞中只表达NK1R-Tr。乳腺癌细胞中NK1R-Tr低表达、NK1R-FL表达增加其对NK1R 和NK2R 受体拮抗剂的敏感度。结论：乳腺组织中NK1R-FL、NK2R 共表达，乳腺癌细胞中NK1R-Tr过表达并负反馈调节NK1R-FL和NK2R 的表达，NK1R 和NK2R 受体可能成为乳腺癌治疗的新靶标。
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| 关 键 词： | 乳腺癌 神经激肽1 受体 神经激肽 2 受体 拮抗剂 |
| 收稿时间： | 2015-10-12 |
| 修稿时间： | 2015-12-07 |
Expression of neurokinin receptors and the effect of their antagonists on human breast cancer |
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| Yunli ZHOU, Meng WANG, Yingna TONG, Xiaobin LIU, Dong DONG, Jie SHAO. Expression of neurokinin receptors and the effect of their antagonists on human breast cancer[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2015, 42(24): 1167-1173. DOI: 10.3969/j.issn.1000-8179.2015.24.112 |
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| Authors: | Yunli ZHOU Meng WANG Yingna TONG Xiaobin LIU Dong DONG Jie SHAO |
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| Affiliation: | Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China |
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| Abstract: | Objective:To determine the expression of the full-length (NK 1R-FL) and truncated (NK1R-Tr) neurokinin-1 receptor (NK 1R) and the neurokinin-2 receptor (NK 2R) in breast cancer tissues and cell lines, as well as to study the effects of the NK1R and NK2R antagonists on the growth of breast cancer cells. Methods: Immunohistochemistry and Western blot assays were used to detect NK1R, NK1R-FL, and NK 2R expression in clinical samples of primary breast cancer tissue, benign lesions, and normal breast tissue, as well as in different breast cancer cell lines. Cell proliferation and soft agar growth tests were performed on cells treated with the NK1R and NK2R antagonists to study the ectopic overexpression of NK 1R-FL and NK1R-Tr in breast cancer cell lines. Results:Total NK 1R expression was detected in the breast cancer tissues, benign lesions, and normal breast tissues. Compared with the normal breast epithe -lia and benign breast lesions, the expression levels of NK 1R-FL and NK2R decreased in the carcinoma. These changes were also relat-ed to the carcinoma type, histological grade, lymph node metastasis, HER 2 and Ki-67expression, and estrogen and progesterone recep -tors in breast cancer. The expression levels of NK 1R-FL and NK 2R were high in the HBL-100 breast cell lines of para-neoplastic tis-sues, but NK1R-Tr expression was low. The MDA-MB- 231, T- 47D, and MCF-7 cells only expressed NK 1R-Tr. NK 1R-Tr or NK 1R-FL overexpression caused the decreased inhibition rate or increased levels of the NK1R and NK2R antagonists in the breast cancer cells. Conclusion:NK1R-FL and NK2R are co-expressed in normal cells. NK 1R-Tr is highly expressed in breast cancer cells and exerts negative feedback to regulate NK 1R-FL and NK2R expression in all cells, especially cancer cells. |
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| Keywords: | breast cancer neurokinin1 receptor neurokinin2 receptor antagonist |
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