doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer阿霉素影响葡糖神经酰胺合成酶的表达在乳腺癌浸润性导管.pdfVIP

Doxorubicin Influences the Expression of Glucosylceramide Synthase in Invasive Ductal Breast Cancer 1 1 1 2 1 1 1 Xiaofang Zhang , Xiaojuan Wu , Peng Su , Yongsheng Gao , Bin Meng , Yanlin Sun , Li Li , 1 1 Zhiqiang Zhou , Gengyin Zhou * 1 Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, P.R. China, 2 Department of Pathology, Academy of Tumor Treatment and Prevention, Jinan, Shandong, P.R.China Abstract Introduction: Glucosylceramide synthase (GCS) is one enzyme that provides a major route for ceramide clearance. Recent evidence has indicated an important role for GCS in multidrug resistance (MDR) tumors. Doxorubicin (DOX)can modulate the expression of GCS in leukemia and ovary cell lines. However, few studies have investigated their relationship in breast cancer; Methods: We collected 84 excision biopsies from patients with invasive ductal breast cancer of whom 33 patients had undergone preoperative chemotherapy. Immunohistochemistry was used to analyze the expression of GCS protein and significantly showed that the expression of GCS was higher in the samples from patients treated with preoperative chemotherapy(p = 0.018). In order to investigate the underlying mechanism, breast cancer cell lines were cultured with different concentrations of DOX, and mRNA and protein levels of GCS were then detected; Results: DOX significantly upregulated the expression of GCS at both the mRNA and protein level in ERa-positive MCF-7 cells.We then block down the Sp1 site of GCS promoter, which inhibited the DOX-mediated increase in GCS expression; and after Era was inhibited in MCF-7 cells, the up-regulation