Ayars Michael, O'Sullivan Eileen, Macgregor-Das Anne, Shindo Koji, Kim Haeryoung, Borges Michael, Yu Jun, Hruban Ralph H, Goggins Michael
Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Oncotarget. 2017 Aug 3;8(48):83370-83383. doi: 10.18632/oncotarget.19848. eCollection 2017 Oct 13.
Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma () encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth .
胰腺导管腺癌由前驱病变发展而来,其中最常见的是胰腺上皮内瘤变(PanIN)。我们对激光捕获显微切割的PanINs和正常胰腺导管细胞进行了RNA测序分析,以鉴定PanINs与正常胰腺导管之间以及低级别和高级别PanINs之间差异表达的基因。在PanIN中鉴定出的表达量最高的转录本之一是编码共同γ链IL2Rγ的白细胞介素2受体亚基γ()。在原位植入的胰腺癌细胞中,CRISPR介导的基因敲除导致小鼠肿瘤生长减弱,原位肿瘤中JAK3表达降低。这些结果表明,IL2Rγ/JAK3信号通路有助于胰腺癌细胞生长。