ATF6 regulates the development of chronic pancreatitis by inducing p53-mediated apoptosis.

Chronic pancreatitis (CP) is a progressive, recurrent inflammatory disorder of the pancreas. Initiation and progression of CP can result from serine protease 1 (PRSS1) overaccumulation and the ensuing endoplasmic reticulum (ER) stress. However, how ER stress pathways regulate the development and progression of CP remains poorly understood. In the present study we aimed to elucidate the ER stress pathway involved in CP. We found high expression of the ER stress marker genes ATF6, XBP1, and CHOP in human clinical specimens. A humanized PRSS1 transgenic mouse was established and treated with caerulein to mimic the development of CP, as evidenced by pathogenic alterations, collagen deposition, and increased expression of the inflammatory factors IL-6, IL-1ß, and TNF-α. ATF6, XBP1, and CHOP expression levels were also increased during CP development in this model. Acinar cell apoptosis was also significantly increased, accompanied by upregulated p53 expression. Inhibition of ATF6 or p53 suppressed the expression of inflammatory factors and progression of CP in the mouse model. Finally, we showed that p53 expression could be regulated by the ATF6/XBP1/CHOP axis to promote the development of CP. We therefore conclude that ATF6 signalling regulates CP progression by modulating pancreatic acinar cell apoptosis, which provides a target for ER stress-based diagnosis and treatment of CP.

[Analysis of epidermal growth factor receptor expression and gene expression status in tissue microarray of cervical squamous cell carcinoma].

OBJECTIVE: To elucidate the protein expression and gene expression status and the relationship between epidermal growth factor receptor (EGFR) protein expression and EGFR gene status. METHODS: Tissue microarray containing 72 cervical squamous cell carcinoma tissues was constructed, and EGFR protein expression and gene status were evaluated by immunohistochemical and fluorescence in situ hybridization (FISH) techniques. RESULTS: Protein expression of EGFR: 69 of 72 cervical squamous cell carcinomas were observed. The results demonstrated it was significant association with invasion depth, lymph node metastasis and lymph-vessel invasion (χ(2) = 4.998, P < 0.05; χ(2) = 4.299, P < 0.05; χ(2) = 4.686, P < 0.05) in cervical squamous cell carcinomas. For FISH assessing EGFR gene, 64 of 72 carcinomas were observed; 7 of 64 cases showed EGFR gene amplification, and 25 disomy, 23 trisomy and 9 polysomy were detected. There were high levels of protein expression in all the EGFR gene amplification cases, and there were significant association between EGFR protein expression and the gene copy number (χ(2) = 13.564, P < 0.05). CONCLUSIONS: EGFR may participate in the occurrence, progression and metastasis of cervical squamous cell carcinoma. Overexpression of EGFR protein may result from gene amplification and gene copy number increases, which showed that EGFR gene expression status may be a more effective biological indicator of cervical squamous cell carcinoma targeted therapy.