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Basic science

1452 - GGNBP2 suppresses tumor growth and cancer stem cell load of triple negative breast cancer by controlling STAT3 pathway


10 Sep 2017


Basic science


Cancer Biology;  Breast Cancer


Jin Zhang


Annals of Oncology (2017) 28 (suppl_5): v1-v21. 10.1093/annonc/mdx361


J. Zhang

Author affiliations

  • The 3rd Department Of Breast Cancer, Tianjin Medical University Cancer Institute & Hospital, 300060 - Tianjin/CN


Abstract 1452


Gametogenetin binding protein 2 (GGNBP2) is encoded in human chromosome 17q12-q23, a region known as a breast and ovarian cancer susceptibility locus. GGNBP2 has a single C2H2 zinc finger and a consensus LxxLL nuclear receptor (NR) binding motif. We have reported that GGNBP2 suppresses ERα-positive breast tumorigenesis by acting as a nuclear receptor co-repressor to restrain ERα activity. However, the detailed molecular mechanisms of GGNBP2 and its role in triple negative breast cancer (TNBC) remain largely unclear.


A human breast cancer tissue array containing 138 human breast tumor tissues were utilized to examine GGNBP2 expression in breast cancer samples by IHC. To address the potential anti-breast tumor activity of GGNBP2 in vitro, we expressed exogenous GGNBP2 in TNBC cells, including MDA-MB-231 and Cal51 cell lines. Cell proliferation and cell cycle were assessed by cell growth curve/EdU assays and flow cytometry after propidium Iodide staining. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays. Cancer stem cell properties were determined by expression of CD44/CD24/ALDH1 markers. The levels of phosphorylated STAT3 and total STAT3 were determined by western blot. Quantitative PCR and Western blot were carried out to evaluate the effects of GGNBP2 overexpression on STAT3 target genes, CCND1, Mcl-1, survivin, bax and bim expression.


GGNBP2 expression is down-regulated in TNBC cells and patient tumors and it is associated with poor patient survival. Overexpression of GGNBP2 significanly induces cell cycle G0/G1 phase arrest and apoptosis in TNBC cell lines. Expression of cancer stem cell markers also decreased in GGNBP2-overexpressed TNBC cells. GGNBP2 reduces the expression levels of CCND1, Mcl-1 and survivin, promotes the expression levels of bax and bim proteins. Importantly, overexpression of GGNBP2 inhibits STAT3 phosphorylation and STAT3 downstream garget gene expression, including CCND1, Mcl-1 and survivin.


GGNBP2 serves as a critical nuclear negative regulator of STAT3-mediated gene expression and tumorigenesis.

Clinical trial identification

Legal entity responsible for the study

Jin Zhang




All authors have declared no conflicts of interest.

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