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PLOS ONE  2013 

TCTP Is an Androgen-Regulated Gene Implicated in Prostate Cancer

DOI: 10.1371/journal.pone.0069398

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TCTP has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. In addition to these intracellular functions, TCTP has extracellular functions and plays an important role in immune cells. TCTP expression was previously shown to be deregulated in prostate cancer, but its function in prostate cancer cells is largely unknown. Here we show that TCTP expression is regulated by androgens in LNCaP prostate cancer cells in vitro as well as human prostate cancer xenografts in vivo. Knockdown of TCTP reduced colony formation and increased apoptosis in LNCaP cells, implicating it as an important factor for prostate cancer cell growth. Global gene expression profiling in TCTP knockdown LNCaP cells showed that several interferon regulated genes are regulated by TCTP, suggesting that it may have a role in regulating immune function in prostate cancer. In addition, recombinant TCTP treatment increased colony formation in LNCaP cells suggesting that secreted TCTP may function as a proliferative factor in prostate cancer. These results suggest that TCTP may have a role in prostate cancer development.


[1]  Jamal K, Patel P, Sooriakumaran P (2008) Minimally invasive surgical modalities in the management of localized prostate cancer. Expert Rev Anticancer Ther 8: 957–966.
[2]  Huggins C, Hodges CV (1941) Studies on prostatic cancer:effect of castration, of estrogen and of androgen injection on serum phosthatases in metastatic carcinoma of the prostate. Cancer Res 1: 293–297.
[3]  Kaarbo M, Kokk TI, Saatcioglu F (2007) Androgen signaling and its interactions with other signaling pathways in prostate cancer. Bioessays 29: 1227–1238.
[4]  Yenofsky R, Bergmann I, Brawerman G (1982) Messenger-Rna Species Partially in a Repressed State in Mouse Sarcoma Ascites-Cells. Proceedings of the National Academy of Sciences of the United States of America-Biological Sciences 79: 5876–5880.
[5]  Nagano-Ito M, Ichikawa S (2012) Biological effects of Mammalian translationally controlled tumor protein (TCTP) on cell death, proliferation, and tumorigenesis. Biochem Res Int 2012: 204960.
[6]  Chan TH, Chen L, Guan XY (2012) Role of translationally controlled tumor protein in cancer progression. Biochem Res Int 2012: 369384.
[7]  Chen SH, Wu PS, Chou CH, Yan YT, Liu H, et al. (2007) A knockout mouse approach reveals that TCTP functions as an essential factor for cell proliferation and survival in a tissue- or cell type-specific manner. Molecular Biology of the Cell 18: 2525–2532.
[8]  Susini L, Besse S, Duflaut D, Lespagnol A, Beekman C, et al.. (2008) TCTP protects from apoptotic cell death by antagonizing bax function. Cell Death Differ.
[9]  Haghighat NG, Ruben L (1992) Purification of Novel Calcium-Binding Proteins from Trypanosoma-Brucei - Properties of 22-Kilodalton, 24-Kilodalton and 38-Kilodalton Proteins. Molecular and Biochemical Parasitology 51: 99–110.
[10]  Kim M, Jung Y, Lee K, Kim C (2000) Identification of the calcium binding sites in translationally controlled tumor protein. Archives of Pharmacal Research 23: 633–636.
[11]  Sanchez JC, Schaller D, Ravier F, Golaz O, Jaccoud S, et al. (1997) Translationally controlled tumor protein: A protein identified in several nontumoral cells including erythrocytes. Electrophoresis 18: 150–155.
[12]  Arcuri F, Papa S, Carducci A, Romagnoli R, Liberatori S, et al. (2004) Translationally controlled tumor protein (TCTP) in the human prostate and prostate cancer cells: Expression, distribution, and calcium binding activity. Prostate 60: 130–140.
[13]  McConkey DJ, Orrenius S (1997) The role of calcium in the regulation of apoptosis. Biochem Biophys Res Commun 239: 357–366.
[14]  Amson R, Pece S, Marine JC, Fiore PP, Telerman A (2013) TPT1/TCTP-regulated pathways in phenotypic reprogramming. Trends Cell Biol 23: 37–46.
[15]  Bommer UA, Borovjagin AV, Greagg MA, Jeffrey IW, Russell P, et al. (2002) The mRNA of the translationally controlled tumor protein P23/TCTP is a highly structured RNA, which activates the dsRNA-dependent protein kinase PKR. RNA 8: 478–496.
[16]  Macdonald SM (2012) Potential role of histamine releasing factor (HRF) as a therapeutic target for treating asthma and allergy. J Asthma Allergy 5: 51–59.
[17]  Macdonald SM, Rafnar T, Langdon J, Lichtenstein LM (1995) Molecular Identification of an IgE-dependent histamine releasing factor. Science 269: 688–690.
[18]  Amzallag N, Passer BJ, Allanic D, Segura E, Thery C, et al. (2004) TSAP6 facilitates the secretion of translationally controlled tumor protein/histamine-releasing factor via a nonclassical pathway. Journal of Biological Chemistry 279: 46104–46112.
[19]  Sirois I, Raymond MA, Brassard N, Cailhier JF, Fedjaev M, et al. (2011) Caspase-3-dependent export of TCTP: a novel pathway for antiapoptotic intercellular communication. Cell Death and Differentiation 18: 549–562.
[20]  Gnanasekar M, Thirugnanam S, Zheng GX, Chen AS, Ramaswamy K (2009) Gene silencing of translationally controlled tumor protein (TCTP) by siRNA inhibits cell growth and induces apoptosis of human prostate cancer cells. International Journal of Oncology 34: 1241–1246.
[21]  Baylot V, Katsogiannou M, Andrieu C, Taieb D, Acunzo J, et al. (2012) Targeting TCTP as a New Therapeutic Strategy in Castration-resistant Prostate Cancer. Molecular Therapy 20: 2244–2256.
[22]  Wainstein MA, He F, Robinson D, Kung HJ, Schwartz S, et al. (1994) CWR22: androgen-dependent xenograft model derived from a primary human prostatic carcinoma. Cancer Res 54: 6049–6052.
[23]  Nagabhushan M, Miller CM, Pretlow TP, Giaconia JM, Edgehouse NL, et al. (1996) CWR22: the first human prostate cancer xenograft with strongly androgen-dependent and relapsed strains both in vivo and in soft agar. Cancer Res 56: 3042–3046.
[24]  Lechner JF, Haugen A, McClendon IA, Pettis EW (1982) Clonal Growth of Normal Adult Human Bronchial Epithelial-Cells in a Serum-Free Medium. In Vitro-Journal of the Tissue Culture Association 18: 633–642.
[25]  Engedal N, Korkmaz CG, Saatcioglu F (2002) C-Jun N-terminal kinase is required for phorbol ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line LNCaP. Oncogene 21: 1017–1027.
[26]  Yang Y, Yang F, Xiong ZY, Yan Y, Wang XM, et al. (2005) An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity. Oncogene 24: 4778–4788.
[27]  Zhang D, Li F, Weidner D, Mnjoyan ZH, Fujise K (2002) Physical and functional interaction between myeloid cell leukemia 1 protein (MCL1) and fortilin - The potential role of MCL1 as a fortilin chaperone. Journal of Biological Chemistry 277: 37430–37438.
[28]  Li F, Zhang D, Fujise K (2001) Characterization of fortilin, a novel antiapoptotic protein. Journal of Biological Chemistry 276: 47542–47549.
[29]  Dysvik B, Jonassen I (2001) J-Express: exploring gene expression data using Java. Bioinformatics 17: 369–370.
[30]  Vonakis BM, Macglashan DW Jr, Vilarino N, Langdon JM, Scott RS, et al. (2008) Distinct characteristics of signal transduction events by histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP)-induced priming and activation of human basophils. Blood 111: 1789–1796.
[31]  Kang HS, Lee MJ, Song H, Han SH, Kim YM, et al. (2001) Molecular identification of IgE-dependent histamine-releasing factor as a B cell growth factor. Journal of Immunology 166: 6545–6554.
[32]  Vonakis BM, Gibbons S, Sora R, Langdon JM, MacDonald SM (2001) Src homology 2 domain-containing inositol 5 ' phosphatase is negatively associated with histamine release to human recombinant histamine-releasing factor in human basophils. Journal of Allergy and Clinical Immunology 108: 822–831.
[33]  Yoneda K, Rokutan K, Nakamura Y, Yanagawa H, Kondo-Teshima S, et al. (2004) Stimulation of human bronchial epithelial cells by IgE-dependent histamine-releasing factor. American Journal of Physiology-Lung Cellular and Molecular Physiology 286: L174–L181.
[34]  Nelson PS (2012) Molecular States Underlying Androgen Receptor Activation: A Framework for Therapeutics Targeting Androgen Signaling in Prostate Cancer. Journal of Clinical Oncology 30: 644–646.
[35]  Malmgaard L (2004) Induction and regulation of IFNs during viral infections. Journal of Interferon and Cytokine Research 24: 439–454.
[36]  Fenner BJ, Scannell M, Prehn JHM (2010) Expanding the Substantial Interactome of NEMO Using Protein Microarrays. Plos One 5.
[37]  Madigan AA, Sobek KM, Cummings JL, Green WR, Bacich DJ, et al. (2012) Activation of innate anti-viral immune response genes in symptomatic benign prostatic hyperplasia. Genes and Immunity 13: 566–572.
[38]  Duarte CW, Willey CD, Zhi D, Cui X, Harris JJ, et al.. (2012) Expression Signature of IFN/STAT1 Signaling Genes Predicts Poor Survival Outcome in Glioblastoma Multiforme in a Subtype-Specific Manner. Plos One 7.
[39]  Coleman IM, Kiefer JA, Brown LG, Pitts TE, Nelson PS, et al. (2006) Inhibition of androgen-independent prostate cancer by estrogenic compounds is associated with increased expression of immune-related genes. Neoplasia 8: 862–878.
[40]  Weichselbaum RR, Ishwaran H, Yoon T, Nuyten DSA, Baker SW, et al. (2008) An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proceedings of the National Academy of Sciences of the United States of America 105: 18490–18495.
[41]  Marra E, Uva P, Viti V, Simonelli V, Dogliotti E, et al.. (2010) Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways. Bmc Cancer 10.
[42]  Heinonen H, Nieminen A, Saarela M, Kallioniemi A, Klefstrom J, et al.. (2008) Deciphering downstream gene targets of PI3K/mTOR/p70S6K pathway in breast cancer. Bmc Genomics 9.


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