Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response
Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response
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DOI：
10.4143/crt.2019.217
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发表时间：
2019-07
期刊：
影响因子：
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通讯作者：
Qiao Xu;Y. Shao;Jinman Zhang;Huikun Zhang;Yawen Zhao;Xiaoli Liu;Zhifang Guo;Wei Chong;Feng Gu;Yongjie Ma
中科院分区：
文献类型：
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作者：
Qiao Xu;Y. Shao;Jinman Zhang;Huikun Zhang;Yawen Zhao;Xiaoli Liu;Zhifang Guo;Wei Chong;Feng Gu;Yongjie Ma
目的前梯度3(AGR3)属于人类前梯度(AGR)家族。AGR3在癌症中的作用尚不清楚。本研究旨在探讨AGR3在乳腺癌浸润性导管癌(IDC)中是否具有预后价值以及是否能促进肿瘤进展。材料与方法采用免疫组织化学方法检测AGR3在乳腺良性病变、导管原位癌和IDC中的表达。分析AGR3‘S与IDC患者临床病理特征及预后的关系。通过细胞功能实验、胶原胶微滴包埋培养药敏试验和细胞毒性分析，检测了AGR3的S对乳腺癌细胞增殖、侵袭能力和化疗药物敏感性的影响。结果AGR3在IDC组织学分级为I~II级的患者中表达上调，并与复发和远处转移的高危因素呈正相关。在乳腺癌细胞株中，AGR3能促进乳腺癌细胞的增殖和侵袭能力，这与临床分析一致。此外，AGR3可提示紫杉烷治疗的乳腺癌患者预后不良，而5-氟嘧啶治疗的乳腺癌患者预后良好。AGR3高表达的乳腺癌细胞对紫杉烷耐药，对5-氟嘧啶敏感。结论AGR3可能是组织学分级为I~II级的管腔B亚型IDC患者的潜在预后指标。AGR3高表达的患者应采用含5-氟嘧啶但不含紫杉烷的化疗方案。
Purpose Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. Materials and Methods AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. Results AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. Conclusion AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.