Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice

Jian Hua Mao; Di Wu; Jesus Perez-Losada; Tao Jiang; Qian Li; Richard M. Neve; Joe W. Gray; Wei Wen Cai; Allan Balmain

doi:10.1016/j.ccr.2006.11.025

Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice

Jian Hua Mao, Di Wu, Jesus Perez-Losada, Tao Jiang, Qian Li, Richard M. Neve, Joe W. Gray, Wei Wen Cai, Allan Balmain

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

Abstract

The Aurora-A kinase gene is amplified in a subset of human tumors and in radiation-induced lymphomas from p53 heterozygous mice. Normal tissues from p53^-/- mice have increased Aurora-A protein levels, but lymphomas from these mice exhibit heterozygous deletions of Aurora-A and/or reduced protein expression. A similar correlation between low p53 levels and Aurora-A gene deletions and expression is found in human breast cancer cell lines. In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status. These data have implications for the design of approaches to targeted cancer therapy involving the crosstalk between Aurora-A kinase and p53 pathways.

Original language	English (US)
Pages (from-to)	161-173
Number of pages	13
Journal	Cancer Cell
Volume	11
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2006.11.025
State	Published - Feb 13 2007
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2006.11.025

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title = "Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice",

abstract = "The Aurora-A kinase gene is amplified in a subset of human tumors and in radiation-induced lymphomas from p53 heterozygous mice. Normal tissues from p53-/- mice have increased Aurora-A protein levels, but lymphomas from these mice exhibit heterozygous deletions of Aurora-A and/or reduced protein expression. A similar correlation between low p53 levels and Aurora-A gene deletions and expression is found in human breast cancer cell lines. In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status. These data have implications for the design of approaches to targeted cancer therapy involving the crosstalk between Aurora-A kinase and p53 pathways.",

author = "Mao, {Jian Hua} and Di Wu and Jesus Perez-Losada and Tao Jiang and Qian Li and Neve, {Richard M.} and Gray, {Joe W.} and Cai, {Wei Wen} and Allan Balmain",

note = "Funding Information: These studies were initially supported by the Commission of the European Communities and the Cancer Research Campaign (UK), and subsequently by NCI grant U01 CA84244 and by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-03ER63630 to A.B. The UCSF Cancer Center Genome Core was essential for the sequencing and study design of TaqMan assay. Special thanks go to the staff of the CRUK Beatson Institute and UCSF Comprehensive Cancer Center animal house for animal husbandry. ",

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doi = "10.1016/j.ccr.2006.11.025",

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AU - Mao, Jian Hua

AU - Wu, Di

AU - Perez-Losada, Jesus

AU - Jiang, Tao

AU - Li, Qian

AU - Neve, Richard M.

AU - Gray, Joe W.

AU - Cai, Wei Wen

AU - Balmain, Allan

N1 - Funding Information: These studies were initially supported by the Commission of the European Communities and the Cancer Research Campaign (UK), and subsequently by NCI grant U01 CA84244 and by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-03ER63630 to A.B. The UCSF Cancer Center Genome Core was essential for the sequencing and study design of TaqMan assay. Special thanks go to the staff of the CRUK Beatson Institute and UCSF Comprehensive Cancer Center animal house for animal husbandry.

PY - 2007/2/13

Y1 - 2007/2/13

N2 - The Aurora-A kinase gene is amplified in a subset of human tumors and in radiation-induced lymphomas from p53 heterozygous mice. Normal tissues from p53-/- mice have increased Aurora-A protein levels, but lymphomas from these mice exhibit heterozygous deletions of Aurora-A and/or reduced protein expression. A similar correlation between low p53 levels and Aurora-A gene deletions and expression is found in human breast cancer cell lines. In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status. These data have implications for the design of approaches to targeted cancer therapy involving the crosstalk between Aurora-A kinase and p53 pathways.

AB - The Aurora-A kinase gene is amplified in a subset of human tumors and in radiation-induced lymphomas from p53 heterozygous mice. Normal tissues from p53-/- mice have increased Aurora-A protein levels, but lymphomas from these mice exhibit heterozygous deletions of Aurora-A and/or reduced protein expression. A similar correlation between low p53 levels and Aurora-A gene deletions and expression is found in human breast cancer cell lines. In vitro studies using mouse embryo fibroblasts demonstrate that inhibition of Aurora-A can have either positive or negative effects on cell growth as a function of p53 status. These data have implications for the design of approaches to targeted cancer therapy involving the crosstalk between Aurora-A kinase and p53 pathways.

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Crosstalk between Aurora-A and p53: Frequent Deletion or Downregulation of Aurora-A in Tumors from p53 Null Mice

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