NDLI: Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients1 2

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Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients1 2

Content Provider	PubMed Central
Author	Tseng, Ruo-chia Lee, Chin-chu Hsu, Han-shui Ching, Tzao Wang, Yi-ching
Abstract	A HIC1-SIRT1-p53 circular loop in which hypermethylation in cancer 1 (HIC1) represses the transcription of SIRT1 that deacetylates and inactivates p53 thus leading to HIC1 inactivation has been identified in cell and animal models. However, the alteration and prognostic effects of HIC1-SIRT1-p53 circular loop have never been demonstrated in human cancer patients. We examine the HIC1-SIRT1-p53 alterations in 118 lung cancer patients to define their etiological roles in tumorigenesis. We found that patients with lung squamous cell carcinoma with low p53 acetylation and SIRT1 expression mostly showed low HIC1 expression, confirming deregulation of HIC1-SIRT1-p53 circular loop in the clinical model. Interestingly, the expression of deleted in breast cancer 1 (DBC1), which blocks the interaction between SIRT1 deacetylase and p53, led to acetylated p53 in patients with lung adenocarcinoma. However, epigenetic alteration of HIC1 promoter by posttranslational modifications of histones and promoter hypermethylation favoring the compacted chromatin production attenuated the transcriptional induction by acetylated p53. Importantly, lung cancer patients with altered HIC1-SIRT1-p53 circular regulation showed poor prognosis. Our data show the first valid clinical evidence of the deregulation of HIC1-SIRT1-p53 loop in lung tumorigenesis and prognosis. Distinct status of p53 acetylation/deacetylation and HIC1 alteration mechanism result from different SIRT1-DBC1 control and epigenetic alteration in lung squamous cell carcinoma and lung adenocarcinoma.
Starting Page	763
File Format	PDF
ISSN	14765586
e-ISSN	14765586
Journal	Neoplasia (New York, N.Y.)
Issue Number	8
Volume Number	11
Language	English
Publisher	Neoplasia Press Inc.
Publisher Date	2009-08-01
Access Restriction	Open
Rights Holder	Neoplasia Press Inc.
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research

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