Role of the SurvivinGene in Pathophysiology

Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
American Journal Of Pathology (Impact Factor: 4.59). 08/2006; 169(1):1-11. DOI: 10.2353/ajpath.2006.060121
Source: PubMed


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.

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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. "
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    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.
    Phytotherapy Research 11/2014; 29(3). DOI:10.1002/ptr.5257 · 2.66 Impact Factor
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    • "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]. "
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    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.
    Molecular vision 11/2012; 18:2758-69. · 1.99 Impact Factor
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    • "It has been reported that it promotes cell proliferation , confers resistance cell death, regulates cell division, modulates apoptotic and non-apoptotic cell death, regulates cell survival in the face of unfavorable milieus and acts as a resistance factor to various anticancer therapies [7] [8] [9]. So targeting the nodal proteins was a better choice than inhibiting single molecules, some strategies to inhibit survivin have been reported, such as antisense oligonucleotides, ribozymes, small interfering RNAs, dominant-negative mutants, but all of these methods targeting survivin were on gene level inhibition [10] [11]. "
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    ABSTRACT: In order to eliminate common side effects to cancer patients and resistance from chemotherapy, a genetic protein TmSm(T34A) was investigated as a sensitizer to doxorubicin. The results indicated TmSm(T34A) enhanced the sensitivity of three breast cancer cell lines to doxorubicin with low dose, and reduced the dose of doxorubicin significantly in contrast to common effective dose. As a synergistic therapy, the TmSm(T34A) also caused strongest apoptotic activity in MCF-7, and the possible molecular mechanisms were explored primarily. The research showed the TmSm(T34A) is promising to be a potential drug in strengthening therapy effects of breast cancer chemotherapy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 02/2012; 66(5):368-72. DOI:10.1016/j.biopha.2011.12.004 · 2.02 Impact Factor
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