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Published in: BMC Cancer 1/2003

Open Access 01-12-2003 | Research article

Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells

Authors: Liza Konnikova, Maciej Kotecki, Mathew M Kruger, Brent H Cochran

Published in: BMC Cancer | Issue 1/2003

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Abstract

Background

Astrocytomas are the most common type of primary central nervous system tumors. They are frequently associated with genetic mutations that deregulate cell cycle and render these tumors resistant to apoptosis. STAT3, signal transducer and activator of transcription 3, participates in several human cancers by inducing cell proliferation and inhibiting apoptosis and is frequently activated in astrocytomas.

Methods

RNA interference was used to knockdown STAT3 expression in human astrocytes and astrocytoma cell lines. The effect of STAT3 knockdown on apoptosis, cell proliferation, and gene expression was then assessed by standard methods.

Results

We have found that STAT3 is constitutively activated in several human astrocytoma cell lines. Knockdown of STAT3 expression by siRNA induces morphologic and biochemical changes consistent with apoptosis in several astrocytoma cell lines, but not in primary human astrocytes. Moreover, STAT3 is required for the expression of the antiapoptotic genes survivin and Bcl-xL in the A172 glioblastoma cell line.

Conclusion

These results show that STAT3 is required for the survival of some astrocytomas. These studies suggest STAT3 siRNA could be a useful therapeutic agent for the treatment of astrocytomas.
Appendix
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Literature
1.
go back to reference Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA: Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001, 15: 1311-1333. 10.1101/gad.891601.CrossRefPubMed Maher EA, Furnari FB, Bachoo RM, Rowitch DH, Louis DN, Cavenee WK, DePinho RA: Malignant glioma: genetics and biology of a grave matter. Genes Dev. 2001, 15: 1311-1333. 10.1101/gad.891601.CrossRefPubMed
2.
go back to reference Rasheed BK, Wiltshire RN, Bigner SH, Bigner DD: Molecular pathogenesis of malignant gliomas. Curr Opin Oncol. 1999, 11: 162-167. 10.1097/00001622-199905000-00004.CrossRefPubMed Rasheed BK, Wiltshire RN, Bigner SH, Bigner DD: Molecular pathogenesis of malignant gliomas. Curr Opin Oncol. 1999, 11: 162-167. 10.1097/00001622-199905000-00004.CrossRefPubMed
3.
go back to reference Prados MD, Levin V: Biology and treatment of malignant glioma. Semin Oncol. 2000, 27: 1-10.PubMed Prados MD, Levin V: Biology and treatment of malignant glioma. Semin Oncol. 2000, 27: 1-10.PubMed
5.
go back to reference Wechsler-Reya R, Scott MP: The developmental biology of brain tumors. Annu Rev Neurosci. 2001, 24: 385-428. 10.1146/annurev.neuro.24.1.385.CrossRefPubMed Wechsler-Reya R, Scott MP: The developmental biology of brain tumors. Annu Rev Neurosci. 2001, 24: 385-428. 10.1146/annurev.neuro.24.1.385.CrossRefPubMed
6.
go back to reference Levin V A S. Leivei, P. H. Gutin: Neoplasms of the central nervous system In Cancer: Principles and practice of oncology. Edited by: V T DeVita S J Hellman SA Rosemberg. 1997, Philadelphia, Lippincott-Raven, 2022-2082. Levin V A S. Leivei, P. H. Gutin: Neoplasms of the central nervous system In Cancer: Principles and practice of oncology. Edited by: V T DeVita S J Hellman SA Rosemberg. 1997, Philadelphia, Lippincott-Raven, 2022-2082.
7.
go back to reference Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J: Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985, 313: 144-147.CrossRefPubMed Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J: Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature. 1985, 313: 144-147.CrossRefPubMed
8.
go back to reference Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997, 275: 1943-1947. 10.1126/science.275.5308.1943.CrossRefPubMed Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science. 1997, 275: 1943-1947. 10.1126/science.275.5308.1943.CrossRefPubMed
9.
go back to reference Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997, 15: 356-362.CrossRefPubMed Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, Langford LA, Baumgard ML, Hattier T, Davis T, Frye C, Hu R, Swedlund B, Teng DH, Tavtigian SV: Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997, 15: 356-362.CrossRefPubMed
10.
go back to reference Ivanchuk SM, Mondal S, Dirks PB, Rutka JT: The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth. J Neurooncol. 2001, 51: 219-229. 10.1023/A:1010632309113.CrossRefPubMed Ivanchuk SM, Mondal S, Dirks PB, Rutka JT: The INK4A/ARF locus: role in cell cycle control and apoptosis and implications for glioma growth. J Neurooncol. 2001, 51: 219-229. 10.1023/A:1010632309113.CrossRefPubMed
11.
go back to reference Ichimura K, Bolin MB, Goike HM, Schmidt EE, Moshref A, Collins VP: Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res. 2000, 60: 417-424.PubMed Ichimura K, Bolin MB, Goike HM, Schmidt EE, Moshref A, Collins VP: Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res. 2000, 60: 417-424.PubMed
12.
go back to reference Reifenberger G, Ichimura K, Reifenberger J, Elkahloun AG, Meltzer PS, Collins VP: Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. Cancer Res. 1996, 56: 5141-5145.PubMed Reifenberger G, Ichimura K, Reifenberger J, Elkahloun AG, Meltzer PS, Collins VP: Refined mapping of 12q13-q15 amplicons in human malignant gliomas suggests CDK4/SAS and MDM2 as independent amplification targets. Cancer Res. 1996, 56: 5141-5145.PubMed
13.
go back to reference Schmidt EE, Ichimura K, Reifenberger G, Collins VP: CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res. 1994, 54: 6321-6324.PubMed Schmidt EE, Ichimura K, Reifenberger G, Collins VP: CDKN2 (p16/MTS1) gene deletion or CDK4 amplification occurs in the majority of glioblastomas. Cancer Res. 1994, 54: 6321-6324.PubMed
14.
go back to reference Ihle JN: STATs: Signal transducers and activators of transcription (review). Cell. 1996, 84: 331-334.CrossRefPubMed Ihle JN: STATs: Signal transducers and activators of transcription (review). Cell. 1996, 84: 331-334.CrossRefPubMed
15.
go back to reference Shuai K, Schindler C, Prezioso VR, Darnell J. E., Jr.: Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992, 258: 1808-1812.CrossRefPubMed Shuai K, Schindler C, Prezioso VR, Darnell J. E., Jr.: Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science. 1992, 258: 1808-1812.CrossRefPubMed
16.
go back to reference Schindler C, Shuai K, Prezioso VR, Darnell J. E., Jr.: Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992, 257: 809-813.CrossRefPubMed Schindler C, Shuai K, Prezioso VR, Darnell J. E., Jr.: Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science. 1992, 257: 809-813.CrossRefPubMed
17.
go back to reference Shuai K, Stark GR, Kerr IM, Darnell J. E., Jr.: A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993, 261: 1744-1746.CrossRefPubMed Shuai K, Stark GR, Kerr IM, Darnell J. E., Jr.: A single phosphotyrosine residue of Stat91 required for gene activation by interferon-gamma. Science. 1993, 261: 1744-1746.CrossRefPubMed
18.
go back to reference Shuai K, Horvath CM, Huang LH, Qureshi SA, Cowburn D, Darnell J. E., Jr.: Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994, 76: 821-828.CrossRefPubMed Shuai K, Horvath CM, Huang LH, Qureshi SA, Cowburn D, Darnell J. E., Jr.: Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions. Cell. 1994, 76: 821-828.CrossRefPubMed
19.
20.
go back to reference Schindler C, Fu XY, Improta T, Aebersold R, Darnell J. E., Jr.: Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992, 89: 7836-7839.CrossRefPubMedPubMedCentral Schindler C, Fu XY, Improta T, Aebersold R, Darnell J. E., Jr.: Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc Natl Acad Sci U S A. 1992, 89: 7836-7839.CrossRefPubMedPubMedCentral
21.
go back to reference Wagner BJ, Hayes TE, Hoban CJ, Cochran BH: The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. Embo J. 1990, 9: 4477-4484.PubMedPubMedCentral Wagner BJ, Hayes TE, Hoban CJ, Cochran BH: The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. Embo J. 1990, 9: 4477-4484.PubMedPubMedCentral
22.
go back to reference Veals SA, Schindler C, Leonard D, Fu XY, Aebersold R, Darnell J. E., Jr., Levy DE: Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992, 12: 3315-3324.CrossRefPubMedPubMedCentral Veals SA, Schindler C, Leonard D, Fu XY, Aebersold R, Darnell J. E., Jr., Levy DE: Subunit of an alpha-interferon-responsive transcription factor is related to interferon regulatory factor and Myb families of DNA-binding proteins. Mol Cell Biol. 1992, 12: 3315-3324.CrossRefPubMedPubMedCentral
23.
go back to reference Stocklin E, Wissler M, Gouilleux F, Groner B: Functional interactions between Stat5 and the glucocorticoid receptor. Nature. 1996, 383: 726-728. 10.1038/383726a0.CrossRefPubMed Stocklin E, Wissler M, Gouilleux F, Groner B: Functional interactions between Stat5 and the glucocorticoid receptor. Nature. 1996, 383: 726-728. 10.1038/383726a0.CrossRefPubMed
24.
go back to reference Ehret GB, Reichenbach P, Schindler U, Horvath CM, Fritz S, Nabholz M, Bucher P: DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. J Biol Chem. 2001, 276: 6675-6688. 10.1074/jbc.M001748200.CrossRefPubMed Ehret GB, Reichenbach P, Schindler U, Horvath CM, Fritz S, Nabholz M, Bucher P: DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. J Biol Chem. 2001, 276: 6675-6688. 10.1074/jbc.M001748200.CrossRefPubMed
25.
go back to reference Takeda K, Akira S: STAT family of transcription factors in cytokine-mediated biological responses. Cytokine Growth Factor Rev. 2000, 11: 199-207. 10.1016/S1359-6101(00)00005-8.CrossRefPubMed Takeda K, Akira S: STAT family of transcription factors in cytokine-mediated biological responses. Cytokine Growth Factor Rev. 2000, 11: 199-207. 10.1016/S1359-6101(00)00005-8.CrossRefPubMed
26.
go back to reference Hirano T, Ishihara K, Hibi M: Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000, 19: 2548-2556. 10.1038/sj.onc.1203551.CrossRefPubMed Hirano T, Ishihara K, Hibi M: Roles of STAT3 in mediating the cell growth, differentiation and survival signals relayed through the IL-6 family of cytokine receptors. Oncogene. 2000, 19: 2548-2556. 10.1038/sj.onc.1203551.CrossRefPubMed
27.
go back to reference Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L: Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998, 334 ( Pt 2): 297-314.CrossRef Heinrich PC, Behrmann I, Muller-Newen G, Schaper F, Graeve L: Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem J. 1998, 334 ( Pt 2): 297-314.CrossRef
28.
go back to reference Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T, Yokota T: STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. Embo J. 1999, 18: 4261-4269. 10.1093/emboj/18.15.4261.CrossRefPubMedPubMedCentral Matsuda T, Nakamura T, Nakao K, Arai T, Katsuki M, Heike T, Yokota T: STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells. Embo J. 1999, 18: 4261-4269. 10.1093/emboj/18.15.4261.CrossRefPubMedPubMedCentral
30.
go back to reference Zhong Z, Wen Z, Darnell J. E., Jr.: Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994, 264: 95-98.CrossRefPubMed Zhong Z, Wen Z, Darnell J. E., Jr.: Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994, 264: 95-98.CrossRefPubMed
31.
go back to reference Rajan P, McKay RD: Multiple routes to astrocytic differentiation in the CNS. J Neurosci. 1998, 18: 3620-3629.PubMed Rajan P, McKay RD: Multiple routes to astrocytic differentiation in the CNS. J Neurosci. 1998, 18: 3620-3629.PubMed
32.
go back to reference Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS, Jove R: Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 1999, 10: 105-115.CrossRefPubMed Catlett-Falcone R, Landowski TH, Oshiro MM, Turkson J, Levitzki A, Savino R, Ciliberto G, Moscinski L, Fernandez-Luna JL, Nunez G, Dalton WS, Jove R: Constitutive activation of Stat3 signaling confers resistance to apoptosis in human U266 myeloma cells. Immunity. 1999, 10: 105-115.CrossRefPubMed
33.
go back to reference Bowman T, Garcia R, Turkson J, Jove R: STATs in oncogenesis. Oncogene. 2000, 19: 2474-2488. 10.1038/sj.onc.1203527.CrossRefPubMed Bowman T, Garcia R, Turkson J, Jove R: STATs in oncogenesis. Oncogene. 2000, 19: 2474-2488. 10.1038/sj.onc.1203527.CrossRefPubMed
34.
go back to reference Grandis JR, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S, Johnson DE, Huang L, He Y, Kim JD: Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci U S A. 2000, 97: 4227-4232. 10.1073/pnas.97.8.4227.CrossRefPubMedPubMedCentral Grandis JR, Drenning SD, Zeng Q, Watkins SC, Melhem MF, Endo S, Johnson DE, Huang L, He Y, Kim JD: Constitutive activation of Stat3 signaling abrogates apoptosis in squamous cell carcinogenesis in vivo. Proc Natl Acad Sci U S A. 2000, 97: 4227-4232. 10.1073/pnas.97.8.4227.CrossRefPubMedPubMedCentral
35.
go back to reference Schuringa JJ, Wierenga AT, Kruijer W, Vellenga E: Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood. 2000, 95: 3765-3770.PubMed Schuringa JJ, Wierenga AT, Kruijer W, Vellenga E: Constitutive Stat3, Tyr705, and Ser727 phosphorylation in acute myeloid leukemia cells caused by the autocrine secretion of interleukin-6. Blood. 2000, 95: 3765-3770.PubMed
36.
go back to reference Badache A, Hynes NE: Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Res. 2001, 61: 383-391.PubMed Badache A, Hynes NE: Interleukin 6 inhibits proliferation and, in cooperation with an epidermal growth factor receptor autocrine loop, increases migration of T47D breast cancer cells. Cancer Res. 2001, 61: 383-391.PubMed
37.
go back to reference Buettner R, Mora LB, Jove R: Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res. 2002, 8: 945-954.PubMed Buettner R, Mora LB, Jove R: Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res. 2002, 8: 945-954.PubMed
38.
go back to reference Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R: Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol. 1998, 18: 2545-2552.CrossRefPubMedPubMedCentral Turkson J, Bowman T, Garcia R, Caldenhoven E, De Groot RP, Jove R: Stat3 activation by Src induces specific gene regulation and is required for cell transformation. Mol Cell Biol. 1998, 18: 2545-2552.CrossRefPubMedPubMedCentral
39.
go back to reference Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell J. E., Jr.: Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol. 1998, 18: 2553-2558.CrossRefPubMedPubMedCentral Bromberg JF, Horvath CM, Besser D, Lathem WW, Darnell J. E., Jr.: Stat3 activation is required for cellular transformation by v-src. Mol Cell Biol. 1998, 18: 2553-2558.CrossRefPubMedPubMedCentral
40.
go back to reference Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R: Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 2002, 62: 6659-6666.PubMed Mora LB, Buettner R, Seigne J, Diaz J, Ahmad N, Garcia R, Bowman T, Falcone R, Fairclough R, Cantor A, Muro-Cacho C, Livingston S, Karras J, Pow-Sang J, Jove R: Constitutive activation of Stat3 in human prostate tumors and cell lines: direct inhibition of Stat3 signaling induces apoptosis of prostate cancer cells. Cancer Res. 2002, 62: 6659-6666.PubMed
41.
go back to reference Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA, Haque SJ: Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene. 2002, 21: 8404-8413. 10.1038/sj.onc.1206047.CrossRefPubMed Rahaman SO, Harbor PC, Chernova O, Barnett GH, Vogelbaum MA, Haque SJ: Inhibition of constitutively active Stat3 suppresses proliferation and induces apoptosis in glioblastoma multiforme cells. Oncogene. 2002, 21: 8404-8413. 10.1038/sj.onc.1206047.CrossRefPubMed
42.
go back to reference Elbashir SM Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplex of 21-nucleotide RNAs mediate RNA interfeerence in cultured mammalian cells. Nature. 2001, 411: 494-498. 10.1038/35078107.CrossRefPubMed Elbashir SM Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplex of 21-nucleotide RNAs mediate RNA interfeerence in cultured mammalian cells. Nature. 2001, 411: 494-498. 10.1038/35078107.CrossRefPubMed
43.
go back to reference Elstein KH, Zucker RM: Comparison of cellular and nuclear flow cytometric techniques for discriminating apoptotic subpopulations. Exp Cell Res. 1994, 211: 322-331. 10.1006/excr.1994.1094.CrossRefPubMed Elstein KH, Zucker RM: Comparison of cellular and nuclear flow cytometric techniques for discriminating apoptotic subpopulations. Exp Cell Res. 1994, 211: 322-331. 10.1006/excr.1994.1094.CrossRefPubMed
44.
go back to reference Chan A, Reiter R, Wiese S, Fertig G, Gold R: Plasma membrane phospholipid asymmetry precedes DNA fragmentation in different apoptotic cell models. Histochem Cell Biol. 1998, 110: 553-558. 10.1007/s004180050317.CrossRefPubMed Chan A, Reiter R, Wiese S, Fertig G, Gold R: Plasma membrane phospholipid asymmetry precedes DNA fragmentation in different apoptotic cell models. Histochem Cell Biol. 1998, 110: 553-558. 10.1007/s004180050317.CrossRefPubMed
45.
go back to reference Zushi S, Shinomura Y, Kiyohara T, Miyazaki Y, Kondo S, Sugimachi M, Higashimoto Y, Kanayama S, Matsuzawa Y: STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells. Int J Cancer. 1998, 78: 326-330. 10.1002/(SICI)1097-0215(19981029)78:3<326::AID-IJC12>3.0.CO;2-4.CrossRefPubMed Zushi S, Shinomura Y, Kiyohara T, Miyazaki Y, Kondo S, Sugimachi M, Higashimoto Y, Kanayama S, Matsuzawa Y: STAT3 mediates the survival signal in oncogenic ras-transfected intestinal epithelial cells. Int J Cancer. 1998, 78: 326-330. 10.1002/(SICI)1097-0215(19981029)78:3<326::AID-IJC12>3.0.CO;2-4.CrossRefPubMed
46.
go back to reference Aoki Y, Feldman GM, Tosato G: Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood. 2003, 101: 1535-1542. 10.1182/blood-2002-07-2130.CrossRefPubMed Aoki Y, Feldman GM, Tosato G: Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. Blood. 2003, 101: 1535-1542. 10.1182/blood-2002-07-2130.CrossRefPubMed
47.
go back to reference Martin S, Toquet C, Oliver L, Cartron PF, Perrin P, Meflah K, Cuillere P, Vallette FM: Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal. J Neurooncol. 2001, 52: 129-139. 10.1023/A:1010689121904.CrossRefPubMed Martin S, Toquet C, Oliver L, Cartron PF, Perrin P, Meflah K, Cuillere P, Vallette FM: Expression of bcl-2, bax and bcl-xl in human gliomas: a re-appraisal. J Neurooncol. 2001, 52: 129-139. 10.1023/A:1010689121904.CrossRefPubMed
48.
go back to reference Kleinschmidt-DeMasters BK, Heinz D, McCarthy PJ, Bobak JB, Lillehei KO, Shroyer AL, Shroyer KR: Survivin in glioblastomas. Protein and messenger RNA expression and comparison with telomerase levels. Arch Pathol Lab Med. 2003, 127: 826-833.PubMed Kleinschmidt-DeMasters BK, Heinz D, McCarthy PJ, Bobak JB, Lillehei KO, Shroyer AL, Shroyer KR: Survivin in glioblastomas. Protein and messenger RNA expression and comparison with telomerase levels. Arch Pathol Lab Med. 2003, 127: 826-833.PubMed
49.
go back to reference Li W, Liang X, Kellendonk C, Poli V, Taub R: STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol Chem. 2002, 277: 28411-28417. 10.1074/jbc.M202807200.CrossRefPubMed Li W, Liang X, Kellendonk C, Poli V, Taub R: STAT3 contributes to the mitogenic response of hepatocytes during liver regeneration. J Biol Chem. 2002, 277: 28411-28417. 10.1074/jbc.M202807200.CrossRefPubMed
50.
go back to reference Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H: Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 1999, 59: 5059-5063.PubMed Niu G, Heller R, Catlett-Falcone R, Coppola D, Jaroszeski M, Dalton W, Jove R, Yu H: Gene therapy with dominant-negative Stat3 suppresses growth of the murine melanoma B16 tumor in vivo. Cancer Res. 1999, 59: 5059-5063.PubMed
51.
go back to reference Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell J. E., Jr.: Stat3 as an oncogene. Cell. 1999, 98: 295-303.CrossRefPubMed Bromberg JF, Wrzeszczynska MH, Devgan G, Zhao Y, Pestell RG, Albanese C, Darnell J. E., Jr.: Stat3 as an oncogene. Cell. 1999, 98: 295-303.CrossRefPubMed
52.
go back to reference Cattaneo E, Magrassi L, De-Fraja C, Conti L, Di Gennaro I, Butti G, Govoni S: Variations in the levels of the JAK/STAT and ShcA proteins in human brain tumors. Anticancer Res. 1998, 18: 2381-2387.PubMed Cattaneo E, Magrassi L, De-Fraja C, Conti L, Di Gennaro I, Butti G, Govoni S: Variations in the levels of the JAK/STAT and ShcA proteins in human brain tumors. Anticancer Res. 1998, 18: 2381-2387.PubMed
53.
go back to reference Thomas CY, Chouinard M, Cox M, Parsons S, Stallings-Mann M, Garcia R, Jove R, Wharen R: Spontaneous activation and signaling by overexpressed epidermal growth factor receptors in glioblastoma cells. Int J Cancer. 2003, 104: 19-27. 10.1002/ijc.10880.CrossRefPubMed Thomas CY, Chouinard M, Cox M, Parsons S, Stallings-Mann M, Garcia R, Jove R, Wharen R: Spontaneous activation and signaling by overexpressed epidermal growth factor receptors in glioblastoma cells. Int J Cancer. 2003, 104: 19-27. 10.1002/ijc.10880.CrossRefPubMed
54.
go back to reference Tchirkov A, Rolhion C, Bertrand S, Dore JF, Dubost JJ, Verrelle P: IL-6 gene amplification and expression in human glioblastomas. Br J Cancer. 2001, 85: 518-522. 10.1054/bjoc.2001.1942.CrossRefPubMedPubMedCentral Tchirkov A, Rolhion C, Bertrand S, Dore JF, Dubost JJ, Verrelle P: IL-6 gene amplification and expression in human glioblastomas. Br J Cancer. 2001, 85: 518-522. 10.1054/bjoc.2001.1942.CrossRefPubMedPubMedCentral
55.
go back to reference Riffkin CD, Gray AZ, Hawkins CJ, Chow CW, Ashley DM: Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are resistant to apoptosis induction. Neuro-oncol. 2001, 3: 229-240.PubMedPubMedCentral Riffkin CD, Gray AZ, Hawkins CJ, Chow CW, Ashley DM: Ex vivo pediatric brain tumors express Fas (CD95) and FasL (CD95L) and are resistant to apoptosis induction. Neuro-oncol. 2001, 3: 229-240.PubMedPubMedCentral
56.
go back to reference Rieger J, Ohgaki H, Kleihues P, Weller M: Human astrocytic brain tumors express AP02L/TRAIL. Acta Neuropathol (Berl). 1999, 97: 1-4. 10.1007/s004010050948.CrossRef Rieger J, Ohgaki H, Kleihues P, Weller M: Human astrocytic brain tumors express AP02L/TRAIL. Acta Neuropathol (Berl). 1999, 97: 1-4. 10.1007/s004010050948.CrossRef
57.
go back to reference Das A, Tan WL, Teo J, Smith DR: Expression of survivin in primary glioblastomas. J Cancer Res Clin Oncol. 2002, 128: 302-306. 10.1007/s00432-002-0343-4.CrossRefPubMed Das A, Tan WL, Teo J, Smith DR: Expression of survivin in primary glioblastomas. J Cancer Res Clin Oncol. 2002, 128: 302-306. 10.1007/s00432-002-0343-4.CrossRefPubMed
58.
go back to reference O'Driscoll L, Linehan R, Clynes M: Survivin: role in normal cells and in pathological conditions. Curr Cancer Drug Targets. 2003, 3: 131-152.CrossRefPubMed O'Driscoll L, Linehan R, Clynes M: Survivin: role in normal cells and in pathological conditions. Curr Cancer Drug Targets. 2003, 3: 131-152.CrossRefPubMed
59.
go back to reference Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001, 411: 494-498. 10.1038/35078107.CrossRefPubMed Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T: Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature. 2001, 411: 494-498. 10.1038/35078107.CrossRefPubMed
60.
go back to reference Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, Herweijer H: Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat Genet. 2002, 32: 107-108. 10.1038/ng944.CrossRefPubMed Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, Herweijer H: Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat Genet. 2002, 32: 107-108. 10.1038/ng944.CrossRefPubMed
61.
go back to reference McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA: RNA interference in adult mice. Nature. 2002, 418: 38-39. 10.1038/418038a.CrossRefPubMed McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA: RNA interference in adult mice. Nature. 2002, 418: 38-39. 10.1038/418038a.CrossRefPubMed
62.
go back to reference Makimura H, Mizuno TM, Mastaitis JW, Agami R, Mobbs CV: Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake. BMC Neurosci. 2002, 3: 18-10.1186/1471-2202-3-18.CrossRefPubMedPubMedCentral Makimura H, Mizuno TM, Mastaitis JW, Agami R, Mobbs CV: Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake. BMC Neurosci. 2002, 3: 18-10.1186/1471-2202-3-18.CrossRefPubMedPubMedCentral
Metadata
Title
Knockdown of STAT3 expression by RNAi induces apoptosis in astrocytoma cells
Authors
Liza Konnikova
Maciej Kotecki
Mathew M Kruger
Brent H Cochran
Publication date
01-12-2003
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2003
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-3-23

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