RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis

Gong Yang, Imelda Mercado-Uribe, Asha S. Multani, Subrata Sen, Ie Ming Shih, Kwong Kwok Wong, David M. Gershenson, Jinsong Liu

Research output: Contribution to journalArticle

Abstract

The oncogene RAS is known to induce genomic instability, leading to cancer development; the underlying mechanism, however, remains poorly understood. To better understand how RAS functions, we measured the activity of the functionally related genes Aurora-A and BRCA2 in ovarian cancer cell lines and tumor samples containing RAS mutations. We found that Aurora-A and BRCA2 inversely controlled RAS-associated genomic instability and ovarian tumorigenesis through regulation of cytokinesis and polyploidization. Overexpression of mutated RAS ablated BRCA2 expression but induced Aurora-A accumulation at the midbody, leading to abnormal cytokinesis and ultimately chromosomal instability via polyploidy in cancer cells. RAS regulates the expression of Aurora-A and BRCA2 through dysregulated protein expression of farnesyl protein transferase β and insulin-like growth factor binding protein 3. Our results suggest that the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigenesis.

Original languageEnglish (US)
Pages (from-to)275-285
Number of pages11
JournalInternational Journal of Cancer
Volume133
Issue number2
DOIs
StatePublished - Jul 15 2013

Fingerprint

Cytokinesis
Genomic Instability
Carcinogenesis
Chromosomal Instability
Insulin-Like Growth Factor Binding Protein 3
Polyploidy
Transferases
Tumor Cell Line
Oncogenes
Ovarian Neoplasms
Neoplasms
Proteins
Mutation
Genes

Keywords

  • Aurora-A
  • BRCA2
  • cytokinesis
  • genomic instability
  • polyploid cancer cells
  • RAS

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis. / Yang, Gong; Mercado-Uribe, Imelda; Multani, Asha S.; Sen, Subrata; Shih, Ie Ming; Wong, Kwong Kwok; Gershenson, David M.; Liu, Jinsong.

In: International Journal of Cancer, Vol. 133, No. 2, 15.07.2013, p. 275-285.

Research output: Contribution to journalArticle

Yang, Gong ; Mercado-Uribe, Imelda ; Multani, Asha S. ; Sen, Subrata ; Shih, Ie Ming ; Wong, Kwong Kwok ; Gershenson, David M. ; Liu, Jinsong. / RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis. In: International Journal of Cancer. 2013 ; Vol. 133, No. 2. pp. 275-285.
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