Yang Youyun, Liu Hailan, Li Zhaomin, Zhao Zijin, Yip-Schneider Michelle, Fan Qipeng, Schmidt C Max, Chiorean E Gabriela, Xie Jingwu, Cheng Liang, Chen Jey-Hsin, Zhang Jian-Ting
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Int J Biochem Mol Biol. 2011 Jan 1;2(1):89-98.
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.
人脂肪酸合酶（FASN）是一种具有多酶活性的同型二聚体蛋白，负责棕榈酸的合成。已发现FASN在多种人类癌症中表达上调，其表达与预后不良相关，可能是通过导致治疗耐药性。在本研究中，我们测试了FASN在人类胰腺癌中表达是否上调，以及其在胰腺癌中的较高表达水平是否导致对吉西他滨和放疗的内在耐药性。我们发现，FASN在人类胰腺癌组织中显著上调，与年龄、性别、种族和肿瘤分期均无相关性。敲低或过表达FASN可显著下调或上调胰腺癌细胞系对吉西他滨和放疗的耐药性。这些发现表明，胰腺癌中FASN表达升高可能通过导致对化疗和放疗的内在耐药性，从而导致胰腺癌治疗失败。
