- The Overexpression of Histone Deacetylase 1 and Its Relationship with p16INK4a Gene Hypermethylation in Pulmonary Squamous Cell Carcinoma and Adenocarcinoma.
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Jong Hyeok Park, Young Seoub Hong, Phil Jo Choi, Na Young Kim, Kyung Eun Lee, Mee Sook Roh
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Korean J Pathol. 2009;43(2):107-112.
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DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.107
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 Abstract
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- BACKGROUND
DNA methylation and histone modification are dynamically linked in the epigenetic control of gene silencing and they play an important role in tumorigenesis.
METHODS
To evaluate the role of histone deacetylase 1 (HDAC1) in the development of lung cancer and the relationship between a HDAC1 overexpression and p16INK4a hypermethylation, we performed immunohistochemical staining for HDAC1 in 76 lung cancer specimens (39 squamous cell carcinomas and 37 adenocarcinomas) that had been previously evaluated for their p16INK4a methylation status by real-time quantitative polymerase chain reaction.
RESULTS
A HDAC1 overexpression (>50% of HDAC1 immunoreactive cells) was detected in 65 (85.5%) out of the 76 cases and it was more frequently seen in the squamous cell carcinomas (97.4%) than in the adenocarcinomas (73.0%) (p=0.002). The incidence of HDAC1 overexpression tended to be higher in the heavy smokers with more than 20 pack-years (p=0.067). Although there was no statistical significance, the frequency of p16INK4a hypermethylation in the cases with a HDAC1 overexpression (27.7%) tended to be higher than that in the cases without a HDAC1 overexpression (9.0%) (p=0.175).
CONCLUSIONS
A HDAC1 overexpression might be involved in lung carcinogenesis, and especially in a subgroup of smoking and squamous cell carcinoma patients, and a HDAC1 overexpression may be associated with p16INK4a hypermethylation.
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Citations
Citations to this article as recorded by  - Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases
Yulia Aleksandrova, Margarita Neganova
International Journal of Molecular Sciences.2023; 24(19): 14766. CrossRef - Microbiome dysbiosis and epigenetic modulations in lung cancer: From pathogenesis to therapy
Faizan Haider Khan, Basharat Ahmad Bhat, Bashir Ahmad Sheikh, Lubna Tariq, Roshan Padmanabhan, Jay Prakash Verma, Amritesh Chandra Shukla, Afshin Dowlati, Ata Abbas
Seminars in Cancer Biology.2022; 86: 732. CrossRef - Histone deacetylase HDAC1 expression correlates with the progression and prognosis of lung cancer
Lin-Lin Cao, Xiaoxu Song, Lin Pei, Lianhua Liu, Hui Wang, Mei Jia
Medicine.2017; 96(31): e7663. CrossRef - The synthesis and evaluation of N1-(4-(2-[18F]-fluoroethyl)phenyl)-N8-hydroxyoctanediamide ([18F]-FESAHA), A PET radiotracer designed for the delineation of histone deacetylase expression in cancer
Brian M. Zeglis, NagaVaraKishore Pillarsetty, Vadim Divilov, Ronald A. Blasberg, Jason S. Lewis
Nuclear Medicine and Biology.2011; 38(5): 683. CrossRef
- Subcellular Localization of p27(kip1) in Breast Cancer and Its Prognostic Significance.
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Sook Hee Hong, Dae Choel Kim, Se Heon Cho, Young Seoub Hong
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Korean J Pathol. 2006;40(3):185-192.
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Abstract
PDF
- BACKGROUND
p27 is a member of the cyclin-dependent kinase (CDK) inhibitors that arrest the progression of the cell cycle; thus, it acts as a tumor suppressor gene. The loss or decrease of p27 protein is frequently seen and this has an independent prognostic potential for many human cancers. p27 is functionally inactivated through accelerated proteolysis and cytoplasmic sequestration. Cytoplasmic mislocalization of p27 by abnormal phosphorylation in the tumor cells doesn't allow it to bind and inhibit nuclear cyclin/CDK targets.
METHODS
We examined the p27 protein expression in 86 cases of invasive ductal carcinoma of the breast via immunohistochemical staining to evaluate the subcellular localization of p27 and its relationship with the clinicopathologic features and the prognostic factors.
RESULTS
The nuclear expression of p27 was noted in 48.9% of the tumors, a combined nuclear and cytoplasmic expression was noted in 20.9%, a cytoplasmic expression was noted in 12.8%, and a negative expression was noted in 17.4%. The decreased nuclear expression and/or cytoplasmic mislocalization of p27 were statistically correlated with the nuclear grade (p=0.001), histologic grade (p=0.036), tumor size (p=0.033), lymph node metastasis (p=0.043), ER (p=0.001), and PR (p=0.001) status, while they were not correlated with patient age, stage, HER2, p53, and Ki67.
CONCLUSIONS
The breast tumors showing both decreased nuclear expression and cytoplasmic mislocalization of p27 are associated with a deranged cell cycle via functional inactivation and also with poor prognostic factors. It is expected that p27 can be a promising anticancer target molecule for the treatment of breast cancer.
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