Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest
Authors: Nan Li
Jianming Qiu
Xuetao Cao
Xiaojian Wang
Taoyong Chen
Hongzhe Li
Bin Liu
Journal: Clinical Cancer Research (2005)
Discipline: CLINICAL MEDICINE
Keywords: breast cancer; hPEBP4; apoptosis; cell cycle; TNF-alpha
Affiliations: Institute of Immunology, Zhejiang University, Hangzhou, PR China.

Abstract:  Purpose: The current therapeutic approach is not so effective in breast cancer patients. Alternative treatment protocols aimed at different targets need to be explored. We recently reported a novel phosphatidylethanolamine-binding protein, human phosphatidylethanolamine-binding protein 4 (hPEBP4), as an antiapoptotic molecule. The finding led us to explore a promising approach for breast cancer therapy via silencing the expression of hPEBP4. Experimental design: hPEBP4 expression in clinical breast specimens was examined by Tissue Microarrays. RNA interference was used to silence hPEBP4 expression in MCF-7 breast carcinoma cells and the effects on cell proliferation, cell cycle progression, apoptosis, as well as underlying mechanisms, were investigated. Results: hPEBP4 was found to be expressed in up to 50% of breast cancers but in only &lt;4% of normal breast tissues. Silencing of hPEBP4 potentiated tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis and cell cycle arrest in MCF-7 cells, which was due to the increased mitogen-activated protein kinase activation and the enhanced phosphatidylethanolamine externalization. Further investigation showed that silencing of hPEBP4 in MCF-7 cells promoted TNF-alpha-induced stability of p53, up-regulation of phospho-p53ser15, p21waf/cip, and Bax, and down-regulation of Bcl-2 and Bcl-xL, which were shown to depend on extracellular signal-regulated kinase 1/2 and c-jun NH2-terminal kinase activation by hPEBP4 silencing. Moreover, the increased proportion of cells in the G0-G1 phase of cell cycle was observed in hPEBP4-silenced MCF-7 cells on TNF-alpha treatment and the expression of cyclin A and cyclin E was down-regulated more significantly. Conclusions: The antiapoptotic effect and the preferential expression pattern in breast cancer tissues make hPEBP4 a new target for breast cancer therapy. Silencing of hPEBP4 expression may be a promising approach for the treatment of breast carcinoma. 

Retracted: No

PubPeer comments:
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 The issues addressed in the Correction had been reported in April 2014, the correction was issued in March 2015 (about 1 year later). The text of the correction reads:  In this article (Clin Cancer Res 2005;11:7545u201353), which was published in the October 15, 2005, issue of Clinical Cancer Research (1), the Western blot panels, flow cytometry, and RT-PCR panels presented in Figs. 1A, 3Bu2013E, 4, 5A and 5E were incorrect. The authors have provided new versions of these figures (below). In addition, the sentence on page 7549 that reads  As shown in Fig. 3D, pretreatment with PD98059 or SP600125 significantly decreased the apoptotic percentage of hPEBP4-silenced MCF7 cells [from 65.1% to 36.7% (PD98059) or 38.2% (SP600125)], should read as follows:  As shown in Fig. 3D, pretreatment with PD98059 or SP600125 significantly decreased the apoptotic percentage of hPEBP4- silenced MCF7 cells [from 53.9% to 37.6% (PD98059) or 42.1% (SP600125)]. These changes do not affect the interpretation or conclusions of this work. The authors regret this error It might be worth exploring the figure issues that I reported to appreciate the extent of  this error . , 
 Original Figure 1A. All eight b-actin bands in this panel appeared to look remarkably similar. Shown in yellow boxes.  , 
 Original Figure 3B, Actin panel. Lanes 2-5 look remarkably similar to lanes 9-12. Shown with red boxes.  , 
 Original Figure 3C. Several areas in the flow cytometry panels appear to be visible multiple times within the same panel, or between panels.  , 
 Original Figure 3D. Several areas in the flow cytometry panels appear to be visible multiple times within the same panel, or between panels.  , 
 Original Figure 3E, Actin panel. Lanes 1-5 appear to be similar to lanes 6-10. Shown with green boxes.  , 
 Figure 4 and 5. Several lanes in Figure 4A (Actin panel), Figure 4B (p53 panel), and 5E (Cyclin A panel, flipped) look remarkably similar (shown with blue and red boxes).  Figure 5A. The two bands shown in the hPEBP4 panel appear to look very similar (shown with pink boxes). Note the air bubble at the bottom left of the band. Two of the three bands in the b-actin panel also appear to look very similar (shown with green boxes).  , 
 #4 The original Fig 3B *[below]* also invites comparison with the actin band of Fig 6B in [Wang et al (2004)] .  ,