Article

Role of the SurvivinGene in Pathophysiology

Tongji University, Shanghai, Shanghai Shi, China
American Journal Of Pathology (Impact Factor: 4.59). 08/2006; 169(1):1-11. DOI: 10.2353/ajpath.2006.060121
Source: PubMed

ABSTRACT

Although the roles of survivin in control of cancer cell division and apoptosis as well as targeting survivin for cancer therapeutics have been extensively explored and reviewed, the pathophysiological role of survivin in normal human cells/organs has not been deeply investigated or sufficiently reviewed. Studies in the latter area, however, appear to be important for the identification of different mechanisms of regulation and function of survivin in normal versus abnormal cells and tissues (including cancer), which might ultimately provide the basis for novel approaches for disease treatment with low toxicity. This Review is intended to summarize current observations in the literature related to the physiological and/or pathological roles for survivin in various normal human cells or organs. Our view of potential future research directions for survivin pertinent to potential therapeutic applications will also be discussed.

Download full-text

Full-text

Available from: Fengzhi Li, Jun 19, 2014
    • "To further decipher the possible mechanisms through which the apoptotic and/or antiproliferation signaling pathways were triggered, we examined the expression levels of certain signal molecules too. Survivin, a unique member of the inhibitors of apoptosis protein family, plays a key role in control of apoptosis and regulation of cell division (Li and Brattain, 2006). Because survivin is expressed in fetal tissues for survival, but not in normal adult tissues, it may form a therapeutic target for treatment of cancer in adults. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Studies have shown chemopreventive and/or chemotherapeutic effects of several curcumin-based combinatorial treatments on colorectal cancer cells. However, their in vivo effects remain unclear. This study has demonstrated the therapeutic effect of curcumin and oxaliplatin, alone or in combination, on subcutaneously xenografted LoVo human colorectal cancer cells in immunodeficient (nu/nu) mice in vivo. Combinatorial administration of curcumin and oxaliplatin evidently inhibited the growth of colorectal cancer in nude mice, which was significantly more effective than either agent alone. Curcumin combined with oxaliplatin treatment induced apoptosis, accompanied by ultrastructural changes and cell cycle arrest in S and G2/M phases. Further mechanism analysis indicated that while the number of apoptotic tumor cells and the expression of Bax, caspase-3, and poly (ADP-ribose) polymerase (PARP) increased significantly, the expression of Bcl-2, survivin, HSP70, pro-caspase-3, and pro-PARP were dramatically suppressed in tumor cells after the treatment with combinatorial curcumin and oxaliplatin for 22 days. Taken together, the present study has demonstrated that administration of combined curcumin and oxaliplatin effectively suppressed colorectal carcinoma in vivo through inducing apoptosis and thus may provide an effective treatment for colorectal carcinoma. Copyright © 2014 John Wiley & Sons, Ltd.
    No preview · Article · Nov 2014 · Phytotherapy Research
  • Source
    • "Survivin exerts its effect by attaching to caspases and other apoptosis proteins that contain baculoviral IAP repeat BIR regions.Jang et al. (2008)have shown that the -31G allele has significantly decreased transcriptional activity compared to that of the -31C allele, which affects the -31G/C polymorphism, has an important role in the predisposition to lung cancer.Xu et al. (2004)have analyzed cancer cell lines and reported that increased survivin gene expression is related to -31G/C polymorphism. Increased expression occurs at both the protein and the messenger RNA levels.Dai et al. (2010)have reported that polymorphisms at the survivin gene promoter region can cause gene modification in NSCLC.in the control of mitosis, cytokinesis, and apoptosis during the embryonic development of cells (Adida et al., 1998;Murphy et al., 2002;Kawamura et al., 2003;Jiang et al., 2005;Li and Brattain, 2006). According to previous data, the -31G/C polymorphism might have a role in the predisposition to lung cancer (Jang et al., 2008) and other malignancies. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lung cancer is the most common cancer worldwide. Survivin is one of the first reported inhibitors of apoptosis proteins, which is an important family of proteins that regulate apoptosis. The survivin gene is located on human chromosome 17q25, which is composed of 142 amino acids. A common polymorphism of the survivin gene promoter -31G/C has been shown to influence cancer risk. This genetic variant has been associated with overexpression of survivin at both protein and mRNA levels in cancer cells. We examined promoter (-31G\C) genotype frequency in a patient group (N = 146), 77.4% GG, 18.5% GC, 4.1% CC, and in a control group (N = 98), 57.1% GG, 34.7% GC, 8.2% CC. These distributions were significantly different. Promoter (-644C\T) genotype frequency in the patient group was 40.4% TT, 48.6% TC, 11% CC, and in the control group it was 551% TT, 40.8% TC, 4.1% CC; these distributions were also significantly different. Individuals carrying the survivin 31 GC genotype and those carrying the survivin 644 CC genotype had a significantly decreased risk of having non-small-cell lung cancer.
    Full-text · Article · Feb 2013 · Genetics and molecular research: GMR
  • Source
    • "The special property of Survivin, which makes this protein different from the rest of the family, resides in its bifunctional role in controlling mitosis and inhibiting cell death. The tight regulation of cell division and cell death makes Survivin a master switch of organ and tissue homeostasis [8], an essential regulator of cell division [9], a modulator of microtubule dynamics and apoptotic and non-apoptotic cell death [10-12], and a stress response factor ensuring continued cell proliferation and survival [13]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Survivin (Birc5) is the smallest member of the inhibitor of apoptosis (IAP) protein family, which regulates the cell cycle/apoptosis balance. The purpose of this study was to examine Survivin expression in the embryonic chick lens, in chick lens epithelial cell cultures, and in the postnatal mouse lens. Survivin expression was examined using a combination of quantitative real-time polymerase chain reaction, western blotting, and immunocytochemistry. To correlate Survivin expression with the timing of proliferation, we determined the profile of cell proliferation in the developing lens using the cell cycle marker proliferating cell nuclear antigen (PCNA) in quantitative western blotting and immunocytochemistry studies. We also examined the expression of PCNA and the extent of denucleation using terminal deoxynucleotidyl transferase (TdT)-mediated biotin-dUTP nick-end labeling (TUNEL) of lentoids (lens fiber-like cells) during chick lens epithelial cell differentiation in vitro. At embryonic day (ED) 4, Survivin immunostaining was present in two pools in lens epithelial cells and fiber cells: cytoplasmic and nuclear. The nuclear staining became more pronounced as the lens epithelial cells differentiated into lens fiber cells. At ED12, Survivin staining was observed in lens fiber cell nuclei containing marginalized chromatin, indicative of early denucleation events. Using western blotting, Survivin expression peaked at ED6, diminishing thereafter. This profile of expression correlated with the events in chick lens epithelial cell cultures: i) increased Survivin expression was associated with an increase in PCNA staining up to day 6 of culture and ii) downregulation of Survivin expression at day 8 of culture was coincident with a dramatic decrease in PCNA staining and an increase in TdT-mediated biotin-dUTP nick-end labeling in lentoids. In early postnatal mouse lenses, Survivin and PCNA were highly expressed and decreased thereafter during postnatal lens maturation. Survivin is expressed during chick and mouse lens development and in chick lens epithelial cell cultures. High levels of Survivin expression correlated with high rates of proliferation of lens epithelial cells at early stages of development. Downregulation of Survivin expression with development and its progressive localization to the nuclei of lens fiber cells was coincident with a decrease in cell proliferation and increased denucleation in differentiating lens fiber cells. These studies suggest an important role for Survivin as a dual regulator of lens epithelial cell proliferation and lens fiber cell differentiation.
    Full-text · Article · Nov 2012 · Molecular vision
Show more