Research article summary (published 30 Jul 2009):

Distinct HIC1-SIRT1-p53 loop deregulation in lung squamous carcinoma and adenocarcinoma patients.

Full 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.

Author information

Author/s: Tseng, Ruo-Chia (RC); Lee, Chin-Chu (CC); Hsu, Han-Shui (HS); Tzao, Ching (C); Wang, Yi-Ching (YC);

Affiliation: Department of Pharmacology, National Cheng Kung University, Tainan 70101, Taiwan, ROC.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neoplasia (New York, N.Y.) (Neoplasia), published in Canada. (Language: eng)

Reference: 2009-Aug; vol 11 (issue 8) : pp 763-70

Dates: Created 2009/08/03; Completed 2009/10/09;

PMID: 19649206, status: MEDLINE (last retrieved date: 10/9/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adenocarcinoma - genetics; metabolism; pathology Blotting, Western Carcinoma, Non-Small-Cell Lung - genetics; metabolism; pathology Carcinoma, Squamous Cell - genetics; metabolism; pathology DNA Methylation Gene Expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Humans Immunohistochemistry

Immunohistochemistry Immunoprecipitation Kruppel-Like Transcription Factors - genetics; metabolism Lung Neoplasms - genetics; metabolism; pathology Polymerase Chain Reaction Prognosis Promoter Regions, Genetic RNA, Messenger - analysis Sirtuins - genetics; metabolism Tumor Suppressor Protein p53 - genetics; metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: HIC1 protein, human (0) ; Kruppel-Like Transcription Factors (0) ; RNA, Messenger (0) ; Tumor Suppressor Protein p53 (0) ; SIRT1 protein, human (EC 3.5.1.-) ; Sirtuins (EC 3.5.1.-)

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