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Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas
Joint Authors
Wang, Tian-Li
Bristow, Robert E.
Davidson, Ben
Zhang, Hui
Visvanathan, Kala
Yap, Kai Lee
Tian, Yuan
Murthy, Vivek
Shih, Ie-Ming
Kuhajda, Francis P.
Ueda, Stefanie M.
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-05-19
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
Our previous reports demonstrated that NAC1, a BTB/POZ domain-containing nuclear protein, upregulates in recurrent ovarian serous carcinoma and participates in developing drug resistance in cancer cells.
The current study applies quantitative proteomics to identify the proteins controlled by NAC1 by comparing the proteomes of SKOV3 cells with and without expression of a dominant negative NAC1 construct, N130.
From the proteins that are downregulated by N130 (upregulated by NAC1), we chose to further characterize fatty acid synthase (FASN).
Similar to change in protein level, the FASN transcript level in SKOV3 cells was significantly reduced by N130 induction or by NAC1 knockdown.
Immunohistochemistry showed that NAC1 and FASN immunointensities in ovarian serous carcinoma tissues had a highly significant correlation (P<.0001).
Moreover, we found that recurrent serous carcinomas exhibited higher FASN immunointensities than their matched primary tumors (P<.001).
Multivariate analysis showed that an FASN staining score of >1 in serous carcinomas was associated with a worse overall survival time (P<.01).
Finally, C93, a new FASN inhibitor, induced massive apoptosis in carboplatin/paclitaxel resistant ovarian cancer cells.
In conclusion, we show that NAC1 is essential for FASN expression in ovarian serous carcinomas and the expression of FASN significantly correlates with tumor recurrence and disease aggressiveness.
The dependence of drug resistant tumor cells on FASN suggests a potential application of FASN-based therapeutics for recurrent ovarian cancer patients.
American Psychological Association (APA)
Ueda, Stefanie M.& Yap, Kai Lee& Davidson, Ben& Tian, Yuan& Murthy, Vivek& Wang, Tian-Li…[et al.]. 2010. Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas. Journal of Oncology،Vol. 2010, no. 2010, pp.1-12.
https://search.emarefa.net/detail/BIM-460351
Modern Language Association (MLA)
Ueda, Stefanie M.…[et al.]. Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas. Journal of Oncology No. 2010 (2010), pp.1-12.
https://search.emarefa.net/detail/BIM-460351
American Medical Association (AMA)
Ueda, Stefanie M.& Yap, Kai Lee& Davidson, Ben& Tian, Yuan& Murthy, Vivek& Wang, Tian-Li…[et al.]. Expression of Fatty Acid Synthase Depends on NAC1 and Is Associated with Recurrent Ovarian Serous Carcinomas. Journal of Oncology. 2010. Vol. 2010, no. 2010, pp.1-12.
https://search.emarefa.net/detail/BIM-460351
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-460351