دورية أكاديمية
p53 is involved in tumor necrosis factor-alpha-induced apoptosis in the human prostatic carcinoma cell line LNCaP.
| العنوان: | p53 is involved in tumor necrosis factor-alpha-induced apoptosis in the human prostatic carcinoma cell line LNCaP. |
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| المؤلفون: | Rokhlin OW; Department of Pathology, The University of Iowa, Iowa City, Iowa, IA 52242, USA., Gudkov AV, Kwek S, Glover RA, Gewies AS, Cohen MB |
| المصدر: | Oncogene [Oncogene] 2000 Apr 06; Vol. 19 (15), pp. 1959-68. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: Basingstoke : Nature Publishing Group Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987- |
| مواضيع طبية MeSH: | Apoptosis*, Prostatic Neoplasms/*pathology , Tumor Necrosis Factor-alpha/*pharmacology , Tumor Suppressor Protein p53/*metabolism, Animals ; Caspases/metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Cytochrome c Group/metabolism ; Humans ; Male ; Mice ; Mice, Nude ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Prostatic Neoplasms/metabolism ; Proteins/metabolism ; Retinoblastoma Protein/metabolism ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53/antagonists & inhibitors ; Up-Regulation |
| مستخلص: | The human prostatic carcinoma cell line LNCaP is sensitive to TNF-alpha treatment and expresses wild-type p53. To analyse the possible role of p53 in TNF-alpha-mediated apoptosis, we generated a derivative of LNCaP, LN-56, expressing a dominant-negative element of p53, GSE56. P53 inactivation in LN-56 was associated with an increased resistance to apoptosis induced by TNF-alpha. Surface expression of TNF-alpha receptors was unchanged in LN-56 compared to LNCaP. TNF-alpha treatment resulted in accumulation of p53 in LNCaP and upregulation of p21/WAF1. Activation of caspase-7 and PARP proteolysis were delayed in LN-56 under TNF-alpha treatment. TNF-alpha-induced apoptosis in LNCaP cells was accompanied by caspase-dependent proteolysis of p21/WAF1 and Rb, which was significantly attenuated in LN-56. Cytochrome c release was induced by TNF-alpha treatment in both cell lines, but caspase-9 was not activated. LNCaP and LN-56 were injected s.c. in nude mice and tumors were identified in all LN-56, but not LNCaP, bearing mice indicating that p53 plays an important role in growth control of prostatic neoplasms. Interestingly, accumulation of p53 in TNF-alpha-treated LNCaP cells was decreased in the presence of the caspase inhibitor Z-VAD-FMK, suggesting a new role of activated caspases in acceleration of p53 response. In summary, these results indicate that p53 is involved in TNF-alpha-mediated apoptosis in LNCaP. |
| معلومات مُعتمدة: | CA 60730 United States CA NCI NIH HHS; CA 75179 United States CA NCI NIH HHS; CA 76673 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (CDKN1A protein, human) 0 (Cdkn1a protein, mouse) 0 (Cyclin-Dependent Kinase Inhibitor p21) 0 (Cyclins) 0 (Cytochrome c Group) 0 (Proteins) 0 (Retinoblastoma Protein) 0 (Tumor Necrosis Factor-alpha) 0 (Tumor Suppressor Protein p53) EC 2.4.2.30 (Parp1 protein, mouse) EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) EC 3.4.22.- (Caspases) |
| تواريخ الأحداث: | Date Created: 20000422 Date Completed: 20000502 Latest Revision: 20161124 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/sj.onc.1203453 |
| PMID: | 10773886 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 0950-9232 |
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| DOI: | 10.1038/sj.onc.1203453 |