title: Role of fatty acid synthase in gemcitabine and radiation resistance of pancreatic cancers.
abstract: Human fatty acid synthase (FASN) is a homo-dimeric protein with multi-enzymatic activity responsible for the synthesis of palmitate. FASN expression has been found to be up-regulated in multiple types of human cancers and its expression correlates with poor prognosis possibly by causing treatment resistance. In this study, we tested if FASN expression is up-regulated in human pancreatic cancers and if its higher expression level in pancreatic cancers causes intrinsic resistance to gemcitabine and radiation. We found that FASN expression is significantly up-regulated in human pancreatic cancer tissues without any correlation to age, sex, race, and tumor stage. Knocking down or over-expressing FASN significantly down- or up-regulate resistance of pancreatic cancer cell lines to both gemcitabine and radiation treatments. These findings imply that the elevated FASN expression in pancreatic cancers may contribute to unsuccessful treatments of pancreatic cancers by causing intrinsic resistance to both chemotherapy and radiation therapy.
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Youyun
authors.initials: Y
authors.lastname: Yang
authors.forename: Hailan
authors.initials: H
authors.lastname: Liu
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Li
authors.forename: Zijin
authors.initials: Z
authors.lastname: Zhao
authors.forename: Michelle
authors.initials: M
authors.lastname: Yip-Schneider
authors.forename: Qipeng
authors.initials: Q
authors.lastname: Fan
authors.forename: C Max
authors.initials: CM
authors.lastname: Schmidt
authors.forename: E Gabriela
authors.initials: EG
authors.lastname: Chiorean
authors.forename: Jingwu
authors.initials: J
authors.lastname: Xie
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Jey-Hsin
authors.initials: JH
authors.lastname: Chen
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Zhang