Abstract: Objective To observe the changes of epithelial specific ETS transcription factor 3 (ESE3) expression in PDAC cell line under hypoxia and glucose deprived conditions, and its effect on the invasive ability of PDAC cells.Methods Pancreatic cancer tissues and 16 adjacent normal pancreas tissues from 99 patients with PDAC who underwent radical surgery from January 2005 to October 2014 in Tianjin Medical University Cancer Hospital were collected.Immunohistochemistry was used to analyze the expression of ESE3 in tumor tissues and adjacent normal tissues, and explore the relationship between ESE3 expression level and survival prognosis in PDAC patients. The relationship between ESE3 mRNA expression level and clinic pathological features of 147 patients with PDAC was further validated in TCGA database.The PANC-1 overexpressing ESE3 stably transfected cell line was constructed and validated. Transwell assay was used to observe the invasive ability of PDAC cells with overexpressing ESE3. The expressions of HIF-1α, GRP78 and ESE3 under hypoxic and glucose deprived conditions were detected by Western blot assay. Results The expression of ESE3 was significantly lower in PDAC tissues than that in normal pancreatic tissues. The low expression of ESE3 was closely related to the shorten of overall survival (OS) and non-recurrence survival (DFS, P＜0.05). The TCGA database demonstrated that ESE3 expression was associated with metastasis (P＜0.05). The invasion ability of PDAC cells was increased under hypoxic and glucose deprived conditions, the expression of ESE3 was decreased, and the expressions of HIF-1α and GRP78 were increased (P＜0.05). Conclusion Under hypoxic and glucose deprived conditions, the expression of ESE3 is decreased in PDAC cells, which promotes PDAC cells invasion.

Key words: pancreatic neoplasms, neoplasm metastasis, cell hypoxia, glucose deprived, ESE3, HIF-1α, GRP78