Heat shock proteins in pancreatic diseases

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Heat shock proteins (HSPs) are chaperone proteins which protect living cells against injury-inducing stimuli. Dysregulated HSP expression has been observed in various disease conditions, including cancer. With use of a knockout and transgenic animal approach as well as with use of standard methods of HSP70 induction, i.e., thermal stress and arsenite administration, it has been shown that HSP70 protects against cell injury and acinar necrosis in experimental animal models of pancreatitis. Animals in which HSP70 is induced prior to caerulein administration in a caerulein model of pancreatitis have reduced disease severity as demonstrated by lower levels of serum amylase, lesser acinar necrosis on histological examination, and decreased neutrophilic infiltration, all of which suggest that HSP70 protects against cell death. Similar to the protective role of HSP70 in the pancreatitis model, HSP70 overexpression has been observed in pancreatic cancer and is believed to protect cancer cells from death. HSP70 is overexpressed at both messenger RNA and protein levels in pancreatic cancer cell lines as compared with normal pancreatic ductal cells. On a more clinical note, HSP70 is present in great abundance in pancreatic cancer clinical specimens as compared with normal pancreatic margins. Inhibition of HSP70 expression in pancreatic cancer cells leads to caspase-dependent apoptotic cell death and is a novel therapeutic modality against pancreatic cancer. Triptolide is a pharmacologic agent which is highly effective at inhibiting HSP70 expression in pancreatic cancer cells and thus at inducing cell death. Moreover, triptolide is excellent at reducing growth as well as locoregional spread of pancreatic tumors in an orthotopic model of pancreatic cancer and has a tremendous potential as a novel therapeutic agent.

Original languageEnglish (US)
Title of host publicationPancreatology
Subtitle of host publicationFrom Bench to Bedside
PublisherSpringer Berlin Heidelberg
Pages1-8
Number of pages8
ISBN (Print)9783642001512
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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