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 language | English (US) |
|---|---|
| Pages (from-to) | 275-285 |
| Number of pages | 11 |
| Journal | International Journal of Cancer |
| Volume | 133 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 15 2013 |
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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 journal › Article
}
TY - JOUR
T1 - RAS promotes tumorigenesis through genomic instability induced by imbalanced expression of Aurora-A and BRCA2 in midbody during cytokinesis
AU - Yang, Gong
AU - Mercado-Uribe, Imelda
AU - Multani, Asha S.
AU - Sen, Subrata
AU - Shih, Ie Ming
AU - Wong, Kwong Kwok
AU - Gershenson, David M.
AU - Liu, Jinsong
PY - 2013/7/15
Y1 - 2013/7/15
N2 - 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.
AB - 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.
KW - Aurora-A
KW - BRCA2
KW - cytokinesis
KW - genomic instability
KW - polyploid cancer cells
KW - RAS
UR - http://www.scopus.com/inward/record.url?scp=84877818524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877818524&partnerID=8YFLogxK
U2 - 10.1002/ijc.28032
DO - 10.1002/ijc.28032
M3 - Article
VL - 133
SP - 275
EP - 285
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -