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Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas

BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression...

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Autores principales: Rahman, M T, Nakayama, K, Rahman, M, Katagiri, H, Katagiri, A, Ishibashi, T, Ishikawa, M, Iida, K, Nakayama, N, Otsuki, Y, Nakayama, S, Miyazaki, K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394978/
https://www.ncbi.nlm.nih.gov/pubmed/22653145
http://dx.doi.org/10.1038/bjc.2012.246
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author Rahman, M T
Nakayama, K
Rahman, M
Katagiri, H
Katagiri, A
Ishibashi, T
Ishikawa, M
Iida, K
Nakayama, N
Otsuki, Y
Nakayama, S
Miyazaki, K
author_facet Rahman, M T
Nakayama, K
Rahman, M
Katagiri, H
Katagiri, A
Ishibashi, T
Ishikawa, M
Iida, K
Nakayama, N
Otsuki, Y
Nakayama, S
Miyazaki, K
author_sort Rahman, M T
collection PubMed
description BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridisation, and clinical data collected by a retrospective chart review. C75, a FASN inhibitor, was used to assess whether this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1 expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene amplification was significantly higher in the high-grade serous histology than in the clear cell histology (P<0.01). NAC1 expression was significantly correlated with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1 expression or high FASN expression significantly correlated with shorter progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN expression in OCCC cell lines. Profound growth inhibition was observed in C75-treated carcinoma cells with FASN overexpression when compared with the response in carcinoma cells without FASN expression. CONCLUSION: These findings indicate that NAC1/FASN overexpression is critical to the growth and survival of a subset of OCCC. The FASN silencing by the C75-induced phenotypes depends on the expression status of the targeted cell line. Therefore, NAC1/FASN pathway-targeted therapy may benefit selected OCCC patients.
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spelling pubmed-33949782013-07-10 Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas Rahman, M T Nakayama, K Rahman, M Katagiri, H Katagiri, A Ishibashi, T Ishikawa, M Iida, K Nakayama, N Otsuki, Y Nakayama, S Miyazaki, K Br J Cancer Translational Therapeutics BACKGROUND: This study examined the clinical significance of NAC1 and the expression level of its potential downstream target fatty acid synthase (FASN) in ovarian clear cell carcinomas (OCCCs), and evaluated the NAC1/FASN pathway as a potential therapeutic target. METHODS: NAC1 and FASN expression and NACC1 gene amplification were assessed in ovarian cancers by immunohistochemistry, fluorescence in situ hybridisation, and clinical data collected by a retrospective chart review. C75, a FASN inhibitor, was used to assess whether this pathway represented a therapeutic target in OCCC. RESULTS: High NAC1 expression was most frequent in clear cell tumours (40.0%:24/60). NACC1 gene amplification was identified in none of the 58 OCCCs. The frequency of NACC1 gene amplification was significantly higher in the high-grade serous histology than in the clear cell histology (P<0.01). NAC1 expression was significantly correlated with FASN expression in both OCCC samples and OCCC cell lines. Either high NAC1 expression or high FASN expression significantly correlated with shorter progression-free and overall survival (P=0.002 and 0.0048). NAC1 overexpression stimulated FASN expression, and NAC1 silencing using siRNA decreased FASN expression in OCCC cell lines. Profound growth inhibition was observed in C75-treated carcinoma cells with FASN overexpression when compared with the response in carcinoma cells without FASN expression. CONCLUSION: These findings indicate that NAC1/FASN overexpression is critical to the growth and survival of a subset of OCCC. The FASN silencing by the C75-induced phenotypes depends on the expression status of the targeted cell line. Therefore, NAC1/FASN pathway-targeted therapy may benefit selected OCCC patients. Nature Publishing Group 2012-07-10 2012-05-31 /pmc/articles/PMC3394978/ /pubmed/22653145 http://dx.doi.org/10.1038/bjc.2012.246 Text en Copyright © 2012 Cancer Research UK https://creativecommons.org/licenses/by-nc-sa/3.0/From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Translational Therapeutics
Rahman, M T
Nakayama, K
Rahman, M
Katagiri, H
Katagiri, A
Ishibashi, T
Ishikawa, M
Iida, K
Nakayama, N
Otsuki, Y
Nakayama, S
Miyazaki, K
Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title_full Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title_fullStr Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title_full_unstemmed Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title_short Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas
title_sort fatty acid synthase expression associated with nac1 is a potential therapeutic target in ovarian clear cell carcinomas
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394978/
https://www.ncbi.nlm.nih.gov/pubmed/22653145
http://dx.doi.org/10.1038/bjc.2012.246
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