title: Doxorubicin influences the expression of glucosylceramide synthase in invasive ductal breast cancer.
abstract: BACKGROUND
  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 ERα-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 Erα was inhibited in MCF-7 cells, the up-regulation of GCS by DOX also been inhibited.
  
  
  CONCLUSIONS
  In conclusion, our data demonstrated the novel finding that DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERα-positive breast cancer cells.
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wu
authors.forename: Peng
authors.initials: P
authors.lastname: Su
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Meng
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhou
authors.forename: Gengyin
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000201:enzymology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005964:Glucosyltransferases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000903:Antibiotics, Antineoplastic; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D004317:Doxorubicin; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase