دورية أكاديمية
siRNA Down-regulation of the PATZ1 Gene in Human Glioma Cells Increases Their Sensitivity to Apoptotic Stimuli.
| العنوان: | siRNA Down-regulation of the PATZ1 Gene in Human Glioma Cells Increases Their Sensitivity to Apoptotic Stimuli. |
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| المؤلفون: | Tritz R; Brain Tumor Program, Sidney Kimmel Cancer Center, San Diego, CA 92121., Mueller BM, Hickey MJ, Lin AH, Gomez GG, Hadwiger P, Sah DW, Muldoon L, Neuwelt EA, Kruse CA |
| المصدر: | Cancer therapy [Cancer Ther] 2008; Vol. 6 (B), pp. 865-876. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Gene Therapy Press Country of Publication: Greece NLM ID: 101174596 Publication Model: Print Cited Medium: Print ISSN: 1543-9135 (Print) NLM ISO Abbreviation: Cancer Ther Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Alimos, Athens, Greece : Gene Therapy Press, 2003- |
| مستخلص: | The PATZ1 gene encodes a transcription factor that belongs to the BTB/POZ group of transcriptional regulators and has been implicated as a transcriptional repressor. We cloned cDNA from glioma cell lines and found they expressed transcript variant 2 of PATZ1. We designed a specific siRNA against PATZ1 and showed that this siRNA, but not a control randomized siRNA, reduced PATZ1 expression in glioma cells as determined by quantitative PCR. In a panel of human glioma cell lines incubated with proapoptotic FasL, those transfected with PATZ1 siRNA displayed reduced cell numbers by the MTT colorimetric assay, relative to those transfected with randomized siRNA. Further studies showed that in 10-08-MG, U-251MG, U-87MG, and T98G cells PATZ1 siRNA significantly increased apoptosis in response to incubation with soluble FasL, as shown by a morphologic acridine orange/ethidium bromide apoptotic assay. Using an apoptosis specific cDNA microarray we further demonstrated that down-regulation of PATZ1 by siRNA resulted in the upregulation of death receptor pro-apoptotic genes including caspase 8 and Death Receptor 5 (DR5) in U-373MG cells. Since DR5 is the receptor for TRAIL we tested whether PATZ1 downregulation also sensitized cells to TRAIL-induced apoptosis and found that PATZ1 siRNA, but not control siRNA, sensitized U-251MG and T98G glioma cells to TRAIL-induced apoptosis. Altogether, these data demonstrate a previously unknown role for the transcription factor PATZ1 in conferring resistance to apoptosis and indicate that modulation of PATZ1 expression may be a therapeutic strategy for gliomas. |
| References: | Neurosurg Rev. 2003 Jul;26(3):145-58. (PMID: 12783270) Oncogene. 2001 Sep 13;20(41):5789-98. (PMID: 11593384) Genes Dev. 1994 Jul 15;8(14):1664-77. (PMID: 7958847) Gene Ther Mol Biol. 2006;10(A):133-146. (PMID: 16810329) J Cell Sci. 2002 Dec 1;115(Pt 23):4671-83. (PMID: 12415011) Oncogene. 2000 Aug 3;19(33):3799-804. (PMID: 10949935) EMBO J. 2004 Aug 4;23(15):3175-85. (PMID: 15272306) J Biol Chem. 2000 Mar 17;275(11):7894-901. (PMID: 10713105) Neuro Oncol. 2001 Oct;3(4):229-40. (PMID: 11584892) N Engl J Med. 2005 Mar 10;352(10):987-96. (PMID: 15758009) J Biol Chem. 2002 Mar 1;277(9):7598-609. (PMID: 11744704) J Immunol. 2003 Oct 15;171(8):3947-54. (PMID: 14530312) J Neurooncol. 2005 Sep;74(3):241-8. (PMID: 16187021) Clin Cancer Res. 2008 Jan 1;14(1):130-8. (PMID: 18172262) Cancer Cell. 2008 Mar;13(3):235-48. (PMID: 18328427) Clin Cancer Res. 2006 Jun 15;12(12):3705-12. (PMID: 16778096) Neuro Oncol. 2004 Apr;6(2):83-95. (PMID: 15134622) Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10717-21. (PMID: 7938017) CA Cancer J Clin. 2000 Jan-Feb;50(1):7-33. (PMID: 10735013) Gene Ther Mol Biol. 2005;9A:89-106. (PMID: 16467915) Cancer Res. 2008 Aug 1;68(15):6271-80. (PMID: 18676851) Cancer Cell. 2002 Aug;2(2):139-48. (PMID: 12204534) J Biol Chem. 2002 Feb 1;277(5):3280-5. (PMID: 11719514) Int J Cancer. 2001 Apr 15;92(2):309-10. (PMID: 11291062) J Pathol. 2008 May;215(1):39-47. (PMID: 18241078) Mol Cancer Res. 2007 Aug;5(8):783-92. (PMID: 17699104) |
| معلومات مُعتمدة: | R21 NS056300 United States NS NINDS NIH HHS; R21 NS056300-01 United States NS NINDS NIH HHS; R21 NS056300-02 United States NS NINDS NIH HHS; R21 NS056300-03 United States NS NINDS NIH HHS |
| تواريخ الأحداث: | Date Created: 20081217 Latest Revision: 20211020 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC2600477 |
| PMID: | 19081762 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1543-9135 |
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