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Fatty acid synthase overexpression confers an independent prognosticator and associates with radiation resistance in nasopharyngeal carcinoma.
MedLine Citation:
PMID:  23208675     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Fatty acid synthase (FASN) is overexpressed in many human cancers and associated with poor prognosis. However, the role of FASN in nasopharyngeal carcinoma (NPC) has not been studied. We evaluated the expression of FASN immunohistochemically in 124 NPC specimens, stratified them into two groups (FASN-high and FASN-low), and examined the correlation with various clinicopathological parameters. In two NPC cell lines, HONE1 and TW01, we targeted the FASN transcript by shRNAi and evaluated the effect on cell proliferation by WST-1 assay and radiation-induced apoptosis by measuring caspase-3 and caspase-7 activation. NPC with high FASN immunoexpression was correlated with advanced pT disease status and worse prognosis in terms of disease-specific survival, metastasis-free survival and local recurrence-free survival, compared to FASN-low group in both univariate and multivariate analyses. In the two NPC cell lines, endogenous FASN expression was significantly higher than the non-tumor keratinocyte, DOK. When the expression of FASN was suppressed by shRNAi, the tumor cells showed decreased cell proliferation and increased apoptosis after radiation. Our results supported FASN as an adverse prognostic marker in NPC, possibly by conferring cell growth advantage and resistance to radiation-induced apoptosis on tumor cells. The inhibition of FASN expression might be investigated as an adjunct in treatment, especially in radiation resistant NPC.
Authors:
Yu-Chien Kao; Sung-Wei Lee; Li-Ching Lin; Li-Tzong Chen; Chung-Hsi Hsing; Han-Ping Hsu; Hsuan-Ying Huang; Yow-Ling Shiue; Tzu-Ju Chen; Chien-Feng Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-4
Journal Detail:
Title:  Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine     Volume:  -     ISSN:  1423-0380     ISO Abbreviation:  Tumour Biol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8409922     Medline TA:  Tumour Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
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