Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma

Loss of p53 tumor suppressor function is a common event in numerous types of human cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). p73, a member of the p53 family gene has striking structural homology and similar interrelated functions with the p53 gene; transactivate p53 responsive...

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Main Authors:	Arief Ichwan, Solachuddin Jauhari, Taher, Muhammad, Masa-Aki, Ikeda
Format:	Conference or Workshop Item
Language:	English
Published:	2011
Subjects:	RK Dentistry
Online Access:	http://irep.iium.edu.my/4141/ http://irep.iium.edu.my/4141/1/Abstract_siRNA-p73_MSPP2011.pdf

id	iium-4141
recordtype	eprints
spelling	iium-41412012-01-12T06:44:00Z http://irep.iium.edu.my/4141/ Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma Arief Ichwan, Solachuddin Jauhari Taher, Muhammad Masa-Aki, Ikeda RK Dentistry Loss of p53 tumor suppressor function is a common event in numerous types of human cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). p73, a member of the p53 family gene has striking structural homology and similar interrelated functions with the p53 gene; transactivate p53 responsive genes, and induce cell cycle arrest or apoptosis. In contrast to p53, p73 is rarely mutated in human cancers. Therefore targeting the p73 pathway of apoptosis could be a candidate approach to treat human cancers. However,certain mutant p53 proteins expressed in HNSCC cells that encode arginine polymorphism at codon 72(72R) have been known to inactivate p73 through physical interaction. We have reported previously that the endogenous mutant p53 protein (p53R248Q) expressed in human HNSCC HSC-4 cells contained 72R polymorphism. Therefore, silencing expression of such endogenous mutant protein may restore the p73 function in suppressing HSC-4 cell growth. Here we show that treatment with small-interfering RNA(siRNA) specific to inhibit the expression of endogenous mutant p53R248Q protein induced apoptosis in HSC-4 cells. Moreover, the expression genes involved in p73-regulated growth arrest and apoptosis were also upregulated, indicating that the apoptotic activity is indeed due to restoration of p73 function. These results also suggest a potential use of siRNA specific for mutant p53 to treat HNSCC. Keywords: HNSCC, gene therapy 2011 Conference or Workshop Item NonPeerReviewed application/pdf en http://irep.iium.edu.my/4141/1/Abstract_siRNA-p73_MSPP2011.pdf Arief Ichwan, Solachuddin Jauhari and Taher, Muhammad and Masa-Aki, Ikeda (2011) Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma. In: 25th Scientific Meeting of The Malaysian Society Of Pharmacology And Physiology, 25-26 May 2011, UPM Serdang, Selangor.
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RK Dentistry
spellingShingle	RK Dentistry Arief Ichwan, Solachuddin Jauhari Taher, Muhammad Masa-Aki, Ikeda Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
description	Loss of p53 tumor suppressor function is a common event in numerous types of human cancer including Head and Neck Squamous Cell Carcinoma (HNSCC). p73, a member of the p53 family gene has striking structural homology and similar interrelated functions with the p53 gene; transactivate p53 responsive genes, and induce cell cycle arrest or apoptosis. In contrast to p53, p73 is rarely mutated in human cancers. Therefore targeting the p73 pathway of apoptosis could be a candidate approach to treat human cancers. However,certain mutant p53 proteins expressed in HNSCC cells that encode arginine polymorphism at codon 72(72R) have been known to inactivate p73 through physical interaction. We have reported previously that the endogenous mutant p53 protein (p53R248Q) expressed in human HNSCC HSC-4 cells contained 72R polymorphism. Therefore, silencing expression of such endogenous mutant protein may restore the p73 function in suppressing HSC-4 cell growth. Here we show that treatment with small-interfering RNA(siRNA) specific to inhibit the expression of endogenous mutant p53R248Q protein induced apoptosis in HSC-4 cells. Moreover, the expression genes involved in p73-regulated growth arrest and apoptosis were also upregulated, indicating that the apoptotic activity is indeed due to restoration of p73 function. These results also suggest a potential use of siRNA specific for mutant p53 to treat HNSCC. Keywords: HNSCC, gene therapy
format	Conference or Workshop Item
author	Arief Ichwan, Solachuddin Jauhari Taher, Muhammad Masa-Aki, Ikeda
author_facet	Arief Ichwan, Solachuddin Jauhari Taher, Muhammad Masa-Aki, Ikeda
author_sort	Arief Ichwan, Solachuddin Jauhari
title	Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
title_short	Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
title_full	Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
title_fullStr	Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
title_full_unstemmed	Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma
title_sort	silencing endogenous mutant p53 using sirna induces p73-mediated apoptosis in human head and neck squamous cell carcinoma
publishDate	2011
url	http://irep.iium.edu.my/4141/ http://irep.iium.edu.my/4141/1/Abstract_siRNA-p73_MSPP2011.pdf
first_indexed	2023-09-18T20:12:15Z
last_indexed	2023-09-18T20:12:15Z
_version_	1777407555542188032

Silencing endogenous mutant P53 Using Sirna Induces P73-Mediated Apoptosis in Human Head And Neck Squamous Cell Carcinoma

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