title: C/EBP ζ targets to neutrophil gelatinase-associated lipocalin (NGAL) as a repressor for metastasis of MDA-MB-231 cells.
abstract: Breast cancer is a leading cause of morbidity in women worldwide. neutrophil gelatinase-associated lipocalin (NGAL), a useful biomarker of ER negative (ER(-)) breast cancer, promotes local tumor invasion and lymph node metastasis. We first identified the distinctive expression of NGAL in two breast cancer cell lines MCF7 and MDA-MB-231 cells, and then confirmed NGAL as a critical inducer of metastasis. Finally, the transcriptional factor CCAAT enhancer-binding proteins ζ (C/EBP ζ) was overexpressed in MDA-MB-231 cells. Consistent with the effect of NGAL knockdown, C/EBP ζ overexpression caused the significant changes that could prevent cell metastasis. C/EBP ζ overexpression induced a strong decrease in NGAL and matrix metalloproteinases (MMPs) expressions as determined by quantitative real time PCR and Western blotting. To identify the potential role of C/EBP ζ on regulating of NGAL in breast cancer, we established the dual-luciferase reporter assay for NGAL in MDA-MB-231 cells cotransfected with C/EBP ζ. Promoter reporter assays determined that C/EBP ζ directly repressed the human NGAL gene promoter activity by inhibiting the NGAL transcription. Taken together, this work identified that the C/EBP ζ overexpression downregulated NGAL to inhibit migration and invasion of breast cancer, which could be used as a novel strategy for breast cancer therapy.
authors: Chinese Academy of Medical Sciences, Tianjing, People's Republic of China.
authors: Lihong
authors: L
authors: Wang
authors: Huawen
authors: H
authors: Li
authors: Jian
authors: J
authors: Wang
authors: Wei
authors: W
authors: Gao
authors: Yani
authors: Y
authors: Lin
authors: Weina
authors: W
authors: Jin
authors: Guoqiang
authors: G
authors: Chang
authors: Ruojun
authors: R
authors: Wang
authors: Qinghua
authors: Q
authors: Li
authors: Li
authors: L
authors: Ma
authors: Tianxiang
authors: T
authors: Pang
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D000209:Acute-Phase Proteins; C497249:DDIT3 protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins; D051742:Transcription Factor CHOP