Open AccessChronic ethanol exposure of human pancreatic normal ductal epithelial cells induces cancer stem cell phenotype through SATB2
Author(s) -
Yu Wei,
Ma Yiming,
Shankar Sharmila,
Srivastava Rakesh K.
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13666
Subject(s) - pancreatic cancer , sox2 , cancer stem cell , stem cell , biology , cancer research , cancer cell , endocrinology , medicine , cancer , microbiology and biotechnology , biochemistry , embryonic stem cell , gene
The incidence of pancreatic cancer is on the rise. Risk factors for pancreatic cancer include alcohol toxicity and metabolic conditions such as obesity, hypertension, dyslipidaemia, insulin resistance and type 2 diabetes. However, the molecular mechanism by which chronic alcohol consumption contributes to pancreatic cancer is not well understood. The purpose of the study was to demonstrate the effects of long‐term chronic ethanol exposure on the transformation of human pancreatic normal ductal epithelial ( HPNE ) cells. Our data showed that ethanol‐transformed HPNE cells were more progressively transformed exhibiting spheroids and colonies, and anchorage‐independent growth. These transformed cells contained high levels of reactive oxygen species and induced SATB 2 expression. Furthermore, during ethanol‐induced cellular transformation, cells gained the phenotypes of cancer stem cells ( CSC s) by expressing pluripotency maintaining factors (Oct4, Sox2, cM yc and KLF 4) and stem cell markers ( CD 24, CD 44 and CD 133). Ethanol‐induced SATB 2 can bind to the promoters of KLF 4, Oct4, cM yc, Sox2, Bcl‐2 and XIAP genes. Suppression of SATB 2 expression in ethanol‐transformed HPNE cells inhibited cell proliferation, colony formation and markers of CSC s and pluripotency. These data suggest that chronic alcohol consumption may contribute toward the development of pancreatic cancer by converting HPNE cells to cancer stem‐like cells.