دورية أكاديمية
p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest.
| العنوان: | p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest. |
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| المؤلفون: | Zhang K; Department of Molecular Pharmacology, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA., Wu J, Wu X, Wang X, Wang Y, Zhou N, Kuo ML, Liu X, Zhou B, Chang L, Ann D, Yen Y |
| المصدر: | Molecular cancer therapeutics [Mol Cancer Ther] 2011 Feb; Vol. 10 (2), pp. 269-78. Date of Electronic Publication: 2011 Jan 07. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research, Inc Country of Publication: United States NLM ID: 101132535 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-8514 (Electronic) Linking ISSN: 15357163 NLM ISO Abbreviation: Mol Cancer Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research, Inc., c2001- |
| مواضيع طبية MeSH: | Cell Cycle/*genetics , Cell Cycle Proteins/*metabolism , Neoplasms/*genetics , Neoplasms/*metabolism , Ribonucleotide Reductases/*metabolism, Animals ; Cell Cycle Proteins/genetics ; Cell Line, Tumor ; Cell Proliferation ; Cyclin D1/metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Damage/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/genetics ; Gene Silencing ; Humans ; KB Cells ; Mice ; Mice, SCID ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Neoplasms/pathology ; Phosphorylation ; Ribonucleotide Reductases/genetics ; Xenograft Model Antitumor Assays |
| مستخلص: | Deregulation of the expression of p53R2, a p53-inducible homologue of the R2 subunit of ribonucleotide reductase, has been found in various human cancer tissues; however, the roles p53R2 plays in cancer progression and malignancy remain controversial. In the present study, we examined changes in gene expression profiles associated with p53R2 in cancer cells, using the analysis of cDNA microarray. Gene set enrichment analysis identified that the gene set regulating cell-cycle progression was significantly enriched in p53R2-silencing human oropharyngeal carcinoma KB cells. Attenuation of p53R2 expression significantly reduced p21 expression and moderately increased cyclin D1 expression in both wild-type p53 cancer cells (KB and MCF-7) and mutant p53 cancer cells (PC3 and MDA-MB-231). Conversely, overexpression of p53R2-GFP resulted in an increase in the expression of p21 and decrease in the expression of cyclin D1, which correlated with reduced cell population in S-phase in vitro and suppressed growth in vivo. Furthermore, the MAP/ERK kinase inhibitor PD98059 partially abolished modulation of p21 and cyclin D1 expression by p53R2. Moreover, under the conditions of nonstress and adriamycin-induced genotoxic stress, attenuation of p53R2 in KB cells significantly increased phosphorylated H2AX, which indicates that attenuation of p53R2 may enhance DNA damage induced by adriamycin. Overall, our study shows that p53R2 may suppress cancer cell proliferation partially by upregulation of p21 and downregulation of cyclin D1; p53R2 plays critical roles not only in DNA damage repair but also in proliferation of cancer cells. |
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| معلومات مُعتمدة: | R01 CA127541 United States CA NCI NIH HHS; R01 CA127541-03 United States CA NCI NIH HHS; CA 127541-01 United States CA NCI NIH HHS |
| المشرفين على المادة: | 0 (CDKN1A protein, human) 0 (Cell Cycle Proteins) 0 (Cyclin-Dependent Kinase Inhibitor p21) 136601-57-5 (Cyclin D1) EC 1.17.4.- (RRM2B protein, human) EC 1.17.4.- (Ribonucleotide Reductases) EC 2.7.11.24 (MAPK1 protein, human) EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) |
| تواريخ الأحداث: | Date Created: 20110111 Date Completed: 20111014 Latest Revision: 20211020 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC3042803 |
| DOI: | 10.1158/1535-7163.MCT-10-0728 |
| PMID: | 21216934 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1538-8514 |
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| DOI: | 10.1158/1535-7163.MCT-10-0728 |