Endoplasmic Reticulum Stress-Associated Chaperones, Bip/GRP78 and Calnexin are Overexpressed in Keratocystic Odontogenic Tumours

Abstract

Objectives Odontogenic keratocysts (OKCs) are developmental cysts that have been reclassified according World Health Organization (WHO), to keratocystic odontogenic tumours (KCOTs), a term that better reflects their neoplastic nature. The aim of present study is to evaluate the induction of stress of the endoplasmic reticulum and execution of the resulting unfolded protein response in keratinocystic odontogenic tumours.Material and MethodsWe analyzed by immunohistochemistry the expression of the chaperones BiP/GRP78 and calnexin in 24 cases of KCOTs. As controls, we have used 9 cases of periapical or radicular cysts (PACs) and 5 cases of Fibromas (FBs). The PACs and the FBs were included in the analysis, as PACs are the most common type of inflammatory odontogenic cysts of and FBs, as lesions of the connective tissue with unaffected epithelium.ResultsAnalysis revealed a strong association between both BiP/GRP78 and calnexin expression and KCOTs: 18 out of 24 (75%) KCOTs expressed BiP/GRP78 as opposed to 1 out of 9 (13%) PACs, and none of 5 FBs evaluated (P < 0.001, x2-test). Calnexin was expressed in 11 out of 24 KCOTs (46%) but only one out of 9 (13%) PACs, and none of the 5 FBs analyzed (P < 0.001, x2-test).ConclusionsStudy results imply that induction of endoplasmic reticulum stress maybe of diagnostic value in keratocystic odontogenic tumours characterization. In addition to recent findings suggesting that endoplasmic reticulum stress plays a causative role in keratinization of epithelia, pharmacological interference with the execution of the unfolded protein response should be considered for the management of keratocystic odontogenic tumours.

Upregulation of heat shock protein 70 and the differential protein expression induced by tumor necrosis factor-alpha enhances migration and inhibits apoptosis of hepatocellular carcinoma cell HepG2

“…A Recent study is reported that calnexin and another ER-associated chaperone GRP78 are overexpressed in keratocystic odontogenic tumors 44. Our results revealed that protein level of HSP70, HSP90 and calnexin were increased in response to TNFα treatment, suggesting that the promoted molecular chaperone expression may play an important role in the evoked prosurvival signals in HepG2 cell.…”

Endoplasmic reticulum stress response in spontaneously hypertensive rats is affected by myocardial ischemia reperfusion injury

“…Glucose-regulated protein 78 (GRP78) is a significant protein involved in the CHOP pathway. GRP78, also known as immunoglobulin heavy chain-binding protein (Bip), is an important glucose-regulated molecular chaperone ( 5 ). Thus, whether the CHOP pathway is induced may be determined through detecting the expression levels of CHOP and GRP78 proteins.…”

PPARα activation alleviates damage to the cytoskeleton during acute myocardial ischemia/reperfusion in rats

“…GRP78, as a co-chaperone of ER stress, may bind unfolded proteins which accumulate in the ER and protect cells against ER dysfunction during the early stages of ER stress. Elevated protein expression of GRP78 was positively associated with the intensity of ER stress ( 31 ). However, overexpression of GRP78 may not be enough to completely prevent ER stress induced by I/R and, subsequently, structural damage and functional disorders may emerge in the myocardium ( 32 ).…”