Journal article
Heat shock proteins in pancreatic diseases
Journal of gastroenterology and hepatology, Vol.23(s1), pp.S42-S45
03/2008
DOI: 10.1111/j.1440-1746.2007.05272.x
PMID: 18336662
Abstract
Heat shock proteins (HSPs) are chaperone proteins that protect living cells against injury-inducing stimuli. Dysregulated expression of HSPs has been observed in various disease conditions including cancer. Using knock-out and transgenic animal approach, as well as standard, methods of heat shock protein 70 (HSP70) induction (i.e. thermal stress and arsenite administration), it has been shown that HSP70 protects against cell injury and acinar necrosis in experimental model of pancreatitis in animals. Animals in which HSP70 is induced prior to cerulein administration in a cerulein model of pancreatitits have reduced severity of pancreatitis, as demonstrated by lower serum amylase, lesser acinar necrosis on histology and decreased neutrophilic infiltration, suggesting that HSP70 is protective against cell death. Similar to the protective role of HSP70 in a pancreatitis model, HSP70 overexpression has been observed in pancreatic cancer and is believed to protect cancer cells from cell death. HSP70 is overexpressed both at mRNA and protein levels in pancreatic cancer cell lines as compared to normal pancreatic ductal cells. On a more clinical note, HSP70 is present in great abundance in pancreatic cancer clinical specimens as compared to normal pancreatic margins. Inhibition of HSP70 expression in pancreatic cancer cells leads to caspase-dependent apoptotie cell death and is a novel therapeutic modality for pancreatic cancer. Triptolide is a pharmacological agent which highly effective inhibiting HSP70 expression in pancreatic cancer cells and thus induces cell death. Moreover, triptolide is highly efficacious in reducing growth as well as locoregioinal spread of pancreatic tumors in an orthotopic model of pancreatic cancer and has tremendous potential as a novel therapeutic agent.
Details
- Title: Subtitle
- Heat shock proteins in pancreatic diseases
- Creators
- Ashok Saluja - University of MinnesotaVikas Dudeja - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Journal of gastroenterology and hepatology, Vol.23(s1), pp.S42-S45
- DOI
- 10.1111/j.1440-1746.2007.05272.x
- PMID
- 18336662
- NLM abbreviation
- J Gastroenterol Hepatol
- ISSN
- 0815-9319
- eISSN
- 1440-1746
- Publisher
- Wiley
- Number of pages
- 4
- Grant note
- R01DK058694 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) CA124723 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) DK072439; DK058694 / NIDDK NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01CA124723 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 03/2008
- Academic Unit
- Anatomy and Cell Biology; Surgery
- Record Identifier
- 9985244680902771
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