中文摘要：

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（neurokinin2re．ceptor，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NKIR（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、NKIR—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、NKIR-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。

英文摘要：

Objective： To determine the expression of the full-length （NK1R-FL） and truncated （NK1R-Tr） neurokinin-1 receptor （NK1R） and the neurokinin-2 receptor （NK2R） 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 NK2R 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 NK1R-FL and NK1R-Tr in breast cancer cell lines. Results： Total NK1R expression was detected in the breast cancer tissues, benign lesions, and normal breast tissues. Compared with the normal breast epithelia and benign breast lesions, the expression levels of NK1R-FL and NK2R decreased in the carcinoma. These changes were also related to the carcinoma type, histological grade, lymph node metastasis, HER2 and Ki-67 expression, and estrogen and progesterone recep- tors in breast cancer. The expression levels of NK1R-FL and NK2R were high in the HBL-100 breast cell lines of para-neoplastic tissues, but NK1R-Tr expression was low. The MDA-MB-231, T-47D, and MCF-7 cells only expressed NK1R-Tr. NK1R-Tr or NK1R-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. NK1R-Tr is highly expressed in breast cancer cells and exerts negative feedback to regulate NK1R-FL and NK2R expression in all cells, especially cancer cells.