2012 Fiscal Year Final Research Report
NAC1 is an actin-binding protein that is essential for effective cytokinesis in cancer cells.
| Project/Area Number |
21791557
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Shimane University |
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Principal Investigator |
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| Project Period (FY) |
2009 – 2012
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| Keywords | 癌 / ゲノム |
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| Research Abstract |
Ovarian cancer remains the most lethal gynecologic malignancy, largely due to the lack of effective chemotherapeutic agents in the se tting of platinum resistant disease. Chemotherapeutic agents targeting critical molecular pathways hold promise for improving survival in these patients. Understanding the critical molecular pathways is central to the development of such agents. With digital karyotyping, we discovered a new amplified oncogene, NAC1. A subsequent clinicopathological and molecular biological analysis of NAC1 suggested that NAC1 could be a potential molecular target in ovarian cancer. Repression of NAC1 induced apoptosis of ovarian cancer cells. Overexpression of NAC1 in cells lacking endogenous NAC1 results in taxane resistance. NAC1 Knock down of NAC1 in taxane resistant ovarian cancer cell lines restores taxane sensitivity. NAC1 dimerization is integral to its function. Base d on the structural analysis of the NAC1 BTB domain, we screened candidate inhibitors of NAC1 dimer formation. We have begun development on a carcinogenic mouse model of NAC1 in which inhibitors will be tested prior to being introduced in the clinical setting.
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[Journal Article] Prognostic and therapeutic impact of amplification of the chr20q13.2 ZNF217 locus in ovarian clear cell carcinoma2012
Author(s)
Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, IidaK, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K
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Journal Title
Cancer
Volume: 118
Pages: 2846-2857
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[Journal Article] Loss of ARID1A expression is related to patient shorter progression free survival and chemoresistance in ovarian clear cell carcinoma2012
Author(s)
Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, IshibashiT, Iida K, Otsuki Y, Nakayama S, Miyazaki K.
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Journal Title
Mod Pathol
Volume: 25
Pages: 282-288
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[Journal Article] Frequent loss of tumor suppressor ARID1A protein expression inadenocarcinomas/adenosquamous carcinomas of the uterine cervix2012
Author(s)
Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama S, Miyazaki K
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Journal Title
Int J Gynecol Cancer
Volume: 22
Pages: 208-212
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[Journal Article] Frequent Mutations of Chromatin Remodeling Gene ARID1A in Ovarian Clear Cell Carcinoma2010
Author(s)
Jones S, Wang TL, Shih IM, Mao TL, Nakayama K, Roden R, Glas R, Slamon D,Diaz LA Jr, Vogelstein B, Kinzler KW, Velculescu VE, Papadopoulos N
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Journal Title
Science
Volume: 330
Pages: 228-231
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[Journal Article] DNA copy numbers profiles in affinity-purified ovarian clear cell carcinoma2010
Author(s)
Kuo KT, Mao TL, Chen X, Feng Y, Nakayama K, Wang Y, Glas R, Ma MJ, Kurman RJ, Shih IeM, Wang TL
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Journal Title
Clin Cancer Res
Volume: 16
Pages: 1997-2008
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