p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest

Keqiang Zhang, Jun Wu, Xiwei Wu, Xiaochen Wang, Yan Wang, Ning Zhou, Mei Ling Kuo, Xiyong Liu, Bingsen Zhou, Lufen Chang, David Ann, Yun Yen

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalMolecular Cancer Therapeutics
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 1 2011
Externally publishedYes

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Cell Cycle Checkpoints
Cyclin D1
Neoplasms
DNA Damage
KB Cells
Doxorubicin
Cell Proliferation
Mitogen-Activated Protein Kinase Kinases
MCF-7 Cells
Oligonucleotide Array Sequence Analysis
S Phase
Transcriptome
DNA Repair
Genes
Cell Cycle
Up-Regulation
Down-Regulation
Carcinoma
Growth
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest. / Zhang, Keqiang; Wu, Jun; Wu, Xiwei; Wang, Xiaochen; Wang, Yan; Zhou, Ning; Kuo, Mei Ling; Liu, Xiyong; Zhou, Bingsen; Chang, Lufen; Ann, David; Yen, Yun.

In: Molecular Cancer Therapeutics, Vol. 10, No. 2, 01.02.2011, p. 269-278.

Research output: Contribution to journalArticle

Zhang, K, Wu, J, Wu, X, Wang, X, Wang, Y, Zhou, N, Kuo, ML, Liu, X, Zhou, B, Chang, L, Ann, D & Yen, Y 2011, 'p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest', Molecular Cancer Therapeutics, vol. 10, no. 2, pp. 269-278. https://doi.org/10.1158/1535-7163.MCT-10-0728
Zhang, Keqiang ; Wu, Jun ; Wu, Xiwei ; Wang, Xiaochen ; Wang, Yan ; Zhou, Ning ; Kuo, Mei Ling ; Liu, Xiyong ; Zhou, Bingsen ; Chang, Lufen ; Ann, David ; Yen, Yun. / p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest. In: Molecular Cancer Therapeutics. 2011 ; Vol. 10, No. 2. pp. 269-278.
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AU - Kuo, Mei Ling

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AU - Ann, David

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