Cancers 2014, 6(2), 998-1019; doi:10.3390/cancers6020998
Article

Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I

email, email, email, email and * email
Received: 6 December 2013; in revised form: 15 March 2014 / Accepted: 3 April 2014 / Published: 23 April 2014
(This article belongs to the Special Issue Heat Shock Proteins in Cancer: Chaperones of Tumorigenesis)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Hereditary Tyrosinemia type 1 (HT1) is a metabolic liver disease caused by genetic defects of fumarylacetoacetate hydrolase (FAH), an enzyme necessary to complete the breakdown of tyrosine. The severe hepatic dysfunction caused by the lack of this enzyme is prevented by the therapeutic use of NTBC (2-[2-nitro-4-(trifluoromethyl)benzoyl] cyclohexane-1,3-dione). However despite the treatment, chronic hepatopathy and development of hepatocellular carcinoma (HCC) are still observed in some HT1 patients. Growing evidence show the important role of heat shock proteins (HSPs) in many cellular processes and their involvement in pathological diseases including cancer. Their survival-promoting effect by modulation of the apoptotic machinery is often correlated with poor prognosis and resistance to therapy in a number of cancers. Here, we sought to gain insight into the pathophysiological mechanisms associated with liver dysfunction and tumor development in a murine model of HT1. Differential gene expression patterns in livers of mice under HT1 stress, induced by drug retrieval, have shown deregulation of stress and cell death resistance genes. Among them, genes coding for HSPB and HSPA members, and for anti-apoptotic BCL-2 related mitochondrial proteins were associated with the hepatocarcinogenetic process. Our data highlight the variation of stress pathways related to HT1 hepatocarcinogenesis suggesting the role of HSPs in rendering tyrosinemia-affected liver susceptible to the development of HCC.
Keywords: Hereditary Tyrosinemia type 1 (HT1); fumarylacetoacetate hydrolase (FAH); NTBC (2-[2-nitro-4-(trifluoromethyl)benzoyl]cyclohexane-1,3-dione); hepatocellular carcinoma (HCC); heat shock proteins (HSPs); apoptosis
PDF Full-text Download PDF Full-Text [1072 KB, uploaded 23 April 2014 09:43 CEST]

Export to BibTeX |
EndNote


MDPI and ACS Style

Angileri, F.; Morrow, G.; Roy, V.; Orejuela, D.; Tanguay, R.M. Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I. Cancers 2014, 6, 998-1019.

AMA Style

Angileri F, Morrow G, Roy V, Orejuela D, Tanguay RM. Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I. Cancers. 2014; 6(2):998-1019.

Chicago/Turabian Style

Angileri, Francesca; Morrow, Geneviève; Roy, Vincent; Orejuela, Diana; Tanguay, Robert M. 2014. "Heat Shock Response Associated with Hepatocarcinogenesis in a Murine Model of Hereditary Tyrosinemia Type I." Cancers 6, no. 2: 998-1019.

Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert