Downregulation of Cohesin Loading Factor Nipped-B-Like Protein (NIPBL) Induces Cell Cycle Arrest, Apoptosis, and Autophagy of Breast Cancer Cell Lines.

BACKGROUND The cohesin loading factor, nipped-B-like protein (NIPBL), is also known as the sister chromatid cohesion 2 (SCC2) human homolog. Recently, we have studied the role of expression levels of NIPBL in cell proliferation and chemotherapy resistance of non-small cell lung cancer (NSCLC) cells in vitro. The aim of this study was to investigate the effects of expression of the cohesin loading factor, NIPBL, on the cell cycle, apoptosis, and autophagy of breast cancer cell lines in vitro. MATERIAL AND METHODS Expression levels of the NIPBL in the breast cancer cell lines, MCF7, Bcap37, MDA-MB 453 and MDA-MB 231, were measured using Western blot and flow cytometry. Small interfering RNA (si-RNA) was used to study the biological functions of NIPBL. The cell counting kit-8 (CCK-8) assay and the colony formation assay were used to measure cell proliferation; the wound scratching assay and transwell chamber assay were used to investigate cell invasion and migration. RESULTS NIPBL gene and protein expression were upregulated in the MCF7 and Bcap37 cells; si-NIPBL transfection inhibited cell proliferation, invasion, and migration of breast cancer cells. Downregulation of NIPBL arrested cells in the G0/G1 phase of the cell cycle and induced apoptosis and autophagy of breast cancer cells through the caspase3 and mammalian target of rapamycin (mTOR) signaling pathways. CONCLUSIONS [color=black]Downregulation of cohesin loading factor NIPBL arrested breast cancer cells in vitro in the G0/G1 phase of the cell cycle and induced apoptosis and autophagy. [/color].

Prognostic significance of mammary Paget's disease in Chinese women: a 10-year, population-based, matched cohort study.

PURPOSE: To explore the prognostic significance of mammary Paget's disease (PD) in breast cancer (BC) patients and to investigate the association between clinical manifestation and outcome in invasive ductal carcinoma patients with PD (PD-IDC). PATIENTS AND METHODS: Eighty-five patients diagnosed with mammary PD with underlying BC from 2006 to 2012 at Zhejiang Cancer Hospital were recruited. A matched group comprised 85 patients diagnosed with BC without PD. Patients were matched according to four variables: stage (0-IV), age at diagnosis (within 5 years), histologic subtype, and the year of surgery. The 74 patients diagnosed with PD-IDC were divided into three groups based on their clinical presentation. RESULTS: Compared with the matched group, the PD group had more HER2 positivity (P<0.01) and hormone receptor negativity (P<0.01), and a worse outcome (Kaplan-Meier analysis, P<0.001 for disease-free survival and P=0.002 for overall survival). Multivariate Cox regression analyses showed that PD was an independent prognostic predictor for BC patients with PD. In addition, the 22 PD-IDC patients who presented with skin lesions in the nipple/areola and a mass in the breast or axilla had a higher risk of disease relapse than patients who presented with a mass in the breast without skin lesions or patients who presented with skin changes without a palpable mass (adjusted hazards ratio, 0.24; 95% CI, 0.08-0.73; P=0.012 and adjusted hazard ratio, 0.30; 95% CI, 0.06-1.40; P=0.124, respectively). CONCLUSION: PD is an independent prognostic indicator of outcome in BC patients with PD. Furthermore, the primary symptoms at presentation may be an available indicator of prognosis in PD-IDC.