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Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response

Cancer Research and Treatment 2020년 52권 1호 p.218 ~ 245
 ( Xu Qiao ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology

 ( Shao Ying ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Zhang Jinman ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Zhang Huikun ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Zhao Yawen ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Liu Xiaoli ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Guo Zhifang ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology
 ( Chong Wei ) - Tianjin Medical University Cancer Institute and Hospital Department of Breast Cancer Pathology
 ( Gu Feng ) - Tianjin Medical University Cancer Institute and Hospital Department of Breast Cancer Pathology
 ( Ma Yongjie ) - Tianjin Medical University Cancer Institute and Hospital Department of Tumor Cell Biology

Abstract


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.

키워드

Anterior gradient 3; Cancer; Prognosis
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