Abstract 5827: Alterations of telomere and SOX9 play key roles on pancreatic carcinogenesis

Abstract

Abstract The morbidity of pancreatic cancer is predicted to increase because of the growing elderly population. In this study, we analyzed alterations of telomere length and SOX9 expression to clarify the relationship between precancerous lesions (pancreatic intraepithelial neoplasia; PanIN), pancreatic cancer and aging. The incidence of PanIN in the elderly patients was 60%. The telomere, which can protect the chromosome ends, was shortened in the following order; pancreatic duct>PanIN-1>PanIN-2>PanIN-3>pancreatic cancer. The telomeres in normal duct epithelium became shorter with aging, and those in cancers were shorter than in controls, suggesting that telomere shortening occurs when histological changes are absent. SOX9, which regulates pancreatic progenitor cells, was the highest in carcinomas, followed by PanIN-3, PanIN-2, PanIN-1, and duct epithelium. SOX9 expression was positively correlated with telomere length in cancer cells. Inhibition of SOX9 using siRNA showed decrease of human telomerase reverse transcriptase (hTERT) expression and decrease of sphere formation in human pancreatic cancer cell lines. In conclusion, upregulation of SOX9 in the duct epithelium, which harbors shortened telomeres, may give rise to PanINs and pancreatic cancers. Citation Format: Yoko Matsuda, Keiko Yamakawa, Yuko Narusawa. Alterations of telomere and SOX9 play key roles on pancreatic carcinogenesis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5827.