Metastasis-suppressing potential of ribonucleotide reductase small subunit p53R2 in human cancer cells

Xiyong Liu, Bingsen Zhou, Lijun Xue, Jennifer Shih, Karen Tye, Wesley Lin, Christina Qi, Peiguo Chu, Frank Un, Wei Wen, Yun Yen

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Purpose: Previous gene transfection studies have shown that the accumulation of human ribonucleotide reductase small subunit M2 (hRRM2) enhances cellular transformation, tumorigenesis, and malignancy potential. The latest identified small subunit p53R2 has 80% homology to hRRM2. Here, we investigate the role of p53R2 in cancer invasion and metastasis. Experimental Design: The immunohistochemistry was conducted on a tissue array including 49 primary and 59 metastatic colon adenocarcinoma samples to determine the relationship between p53R2 expression and metastasis. A Matrigel invasive chamber was used to sort the highly invasive cells and to evaluate the invasion potential of p53R2. Results: Univariate and multivariate analyses revealed that p53R2 is negatively related to the metastasis of colon adenocarcinoma samples (odds ratio, 0.23; P < 0.05). The decrease of p53R2 is associated with cell invasion potential, which was observed in both p53 wild-type (KB) and mutant (PC-3 and Mia PaCa-2) cell lines. An increase in p53R2 expression by gene transfection significantly reduced the cellular invasion potential to 54% and 30% in KB and PC-3 cells, respectively, whereas inhibition of p53R2 by short interfering RNA resulted in a 3-fold increase in cell migration. Conclusions: Opposite regulation of hRRM2 and p53R2 in invasion potential might play a critical role in determining the invasion and metastasis phenotype in cancer cells. The expression level of ribonucleotide reductase small subunits may serve as a biomarker to predict the malignancy potential of human cancers in the future.

Original languageEnglish
Pages (from-to)6337-6344
Number of pages8
JournalClinical Cancer Research
Volume12
Issue number21
DOIs
Publication statusPublished - Nov 1 2006
Externally publishedYes

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Ribonucleotide Reductases
Neoplasm Metastasis
Neoplasms
Transfection
Colon
Adenocarcinoma
Small Interfering RNA
Cell Movement
Carcinogenesis
Research Design
Multivariate Analysis
Biomarkers
Immunohistochemistry
Odds Ratio
Phenotype
Gene Expression
Cell Line
Genes
ribonucleotide reductase M2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Metastasis-suppressing potential of ribonucleotide reductase small subunit p53R2 in human cancer cells. / Liu, Xiyong; Zhou, Bingsen; Xue, Lijun; Shih, Jennifer; Tye, Karen; Lin, Wesley; Qi, Christina; Chu, Peiguo; Un, Frank; Wen, Wei; Yen, Yun.

In: Clinical Cancer Research, Vol. 12, No. 21, 01.11.2006, p. 6337-6344.

Research output: Contribution to journalArticle

Liu, X, Zhou, B, Xue, L, Shih, J, Tye, K, Lin, W, Qi, C, Chu, P, Un, F, Wen, W & Yen, Y 2006, 'Metastasis-suppressing potential of ribonucleotide reductase small subunit p53R2 in human cancer cells', Clinical Cancer Research, vol. 12, no. 21, pp. 6337-6344. https://doi.org/10.1158/1078-0432.CCR-06-0799
Liu, Xiyong ; Zhou, Bingsen ; Xue, Lijun ; Shih, Jennifer ; Tye, Karen ; Lin, Wesley ; Qi, Christina ; Chu, Peiguo ; Un, Frank ; Wen, Wei ; Yen, Yun. / Metastasis-suppressing potential of ribonucleotide reductase small subunit p53R2 in human cancer cells. In: Clinical Cancer Research. 2006 ; Vol. 12, No. 21. pp. 6337-6344.
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AU - Tye, Karen

AU - Lin, Wesley

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