Elizabeth T Chang

University of Maryland, Baltimore, Baltimore, MD, United States

Are you Elizabeth T Chang?

Claim your profile

Publications (6)38.36 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Survivin, a member of the IAP (inhibitor of apoptosis protein) family, plays important roles in maintaining cellular homoeostasis and regulating cell-cycle progression. This IAP is overexpressed in oesophageal cancer cells, leading to uncontrolled cell growth and resistance to apoptosis. CUG-BP1 (CUG-binding protein 1) is an RNA-binding protein that regulates the stability and translational efficiency of target mRNAs. In the present paper, we report that CUG-BP1 is overexpressed in oesophageal cancer cell lines and human oesophageal cancer specimens. CUG-BP1 associates with the 3'-untranslated region of survivin mRNA, thereby stabilizing the transcript and elevating its expression in oesophageal cancer cells. Our results show that overexpression of CUG-BP1 in oesophageal epithelial cells results in increased survivin mRNA stability and consequently survivin protein expression. Conversely, silencing CUG-BP1 in oesophageal cancer cells destabilizes survivin mRNA, lowering the level of survivin protein. In addition, we have found that altering CUG-BP1 expression modulates susceptibility to chemotherapy-induced apoptosis. Overexpression of CUG-BP1 in oesophageal epithelial cells increases resistance to apoptosis, whereas silencing CUG-BP1 makes oesophageal cancer cells more susceptible to chemotherapy-induced apoptosis. Co-transfection experiments with small interfering RNA directed against survivin suggest that the anti-apoptotic role for CUG-BP1 is not entirely dependent on its effect on survivin expression.
    Biochemical Journal 05/2012; 446(1):113-23. · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Overexpression of survivin, a member of the IAP (inhibitor of apoptosis) family, has been correlated with poorer outcomes in multiple malignancies, including oesophageal cancer. The regulatory mechanisms, particularly at the post-transcriptional level, involved in survivin overexpression are not well understood. Previous work from our group has shown that the RNA-binding protein HuR (Hu antigen R), which is also overexpressed in several malignancies, stabilizes the mRNA of XIAP (X-linked IAP), another IAP family member. In the present study, we demonstrate the binding of HuR to a 288 bp fragment in the 3'-UTR (untranslated region) of survivin mRNA in human oesophageal epithelial cells. Unexpectedly, overexpression of HuR led to a decrease in survivin expression. This was associated with decreased survivin mRNA and promoter activity, suggesting a decrease in transcription. Levels of p53, a negative transcriptional regulator of survivin, increased following HuR overexpression, in conjunction with enhanced p53 mRNA stability. Silencing p53 prior to HuR overexpression resulted in increased survivin protein and mRNA stability. These results demonstrate that, in the absence of p53, HuR overexpression results in increased survivin mRNA stability and protein expression. This provides an additional explanation for the increased survivin expression observed in oesophageal cancer cells that have lost p53.
    Biochemical Journal 03/2011; 437(1):89-96. · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intestinal epithelial cells (IECs) within crypts continuously divide and differentiate as they migrate up towards the luminal surface of the mucosa. With the onset of differentiation, IECs lose their proliferative potential, but the exact mechanism remains unknown. This current study examined the involvement of the TGF-β signaling pathway in this process. Studies were conducted in the IEC-6 cell line derived from rat small intestinal crypt cells. Cell differentiation was induced by forced expression of the Cdx2 gene, a transcription factor responsible for controlling intestinal epithelial cell differentiation. Forced expression of the Cdx2 gene in stable Cdx2-transfected IEC-6 cells resulted in a differentiated phenotype as indicated by morphological features and increased expression of sucrase-isomaltase. Levels of TGF-β type I receptor (TGFβ-RI) and TGF-β type II receptor (TGFβ-RII) increased in these differentiated epithelial cells. The induced TGFβ-RI and TGFβ-RII expression in Cdx2-transfected IEC-6 cells was associated with increased sensitivity to TGF-β-induced growth inhibition. Depletion of cellular polyamines further increased TGF-β receptor expression and additionally enhanced the response to TGF-β-induced growth inhibition. Increased TGFβ-RI and RII in polyamine-deficient cells were also associated with an induction in JunD/AP-1 activity. These results indicate that the loss of the proliferative potential in differentiated IECs results partially from the increased expression of TGF-β receptors.
    International journal of clinical and experimental medicine 01/2011; 4(4):299-308.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Survivin, an important inhibitor of apoptosis, is overexpressed in esophageal cancer and negatively affects survival. The complex regulation of survivin transcription involves enhancement by beta-catenin and repression by p53. The purpose of this study is to test whether inhibition of beta-catenin or overexpression of p53 can decrease survivin expression and render esophageal cancer cells more susceptible to apoptosis. Studies were performed in normal human esophageal epithelial cells and the human esophageal cancer cell line TE7. Levels of beta-catenin, survivin, and p53 were measured by Western blot. Apoptosis was induced after treatment with camptothecin and measured by release of caspase 3 and morphologic criteria. The roles of survivin and beta-catenin in preventing apoptosis were tested by their silencing with specific small interfering RNA molecules. The effect of p53 overexpression on survivin promoter activity was measured using a survivin promoter-luciferase reporter construct and by real-time polymerase chain reaction measurement of survivin mRNA levels. Both beta-catenin and survivin are overexpressed in TE7 cells, whereas p53 expression is negligible. TE7 cells demonstrate resistance to camptothecin-induced apoptosis (P < .01). This effect is significantly reduced by inhibition of survivin, but not of beta-catenin (P < .01). Overexpression of p53 in TE7 cells reduces survivin transcription and mRNA levels (P < .01), without reducing survivin protein levels. Survivin plays a critical role in TE7 cell resistance to camptothecin-induced apoptosis. This effect is not dependent on beta-catenin expression. Overexpression of p53 decreases survivin transcription but does not decrease levels of survivin protein, suggesting posttranscriptional control of survivin expression.
    The Journal of thoracic and cardiovascular surgery 03/2010; 140(1):225-32. · 3.41 Impact Factor
  • Elizabeth Tsu-Ying Chang, James Donahue, Jian-Ying Wang, Richard Battafarano
    Gastroenterology 01/2010; 138(5). · 12.82 Impact Factor
  • Gastroenterology 01/2009; 136(5). · 12.82 Impact Factor