title: ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine             on MICB shedding in PANC-1 pancreatic cancer cells.
abstract: The aim of this study was to investigate the role of ADAM15 in MHC class             I polypeptide-related sequence B (MICB) protein ectodomain shedding and observe             whether or not gemcitabine affects MICB shedding from PANC-1 cells. In this study,             immunohistochemistry of MICB and ADAM15 were performed on tumor samples obtained             from 93 patients with pancreatic ductal adenocarcinoma (PDAC). The expression             of MICB and ADAM15 in the PDAC tissues was significantly higher compared with             that in the normal tissues of the pancreas. Statistical analysis showed a significant             correlation between the expression of MICB and certain classic clinicopathological             characteristics (i.e., histological grade and TNM stage). ADAM15 expression was             found to correlate with lymph node metastasis and TNM stage. The Spearman's rank             test suggested that the expression of MICB was inversely correlated with that             of ADAM15 in PDAC tissues. Knockdown of ADAM15 in PANC-1 cells clearly upregulated             MICB expression on the cellular surface and downregulated soluble MICB (sMICB)             levels in the culture supernatants. A non-toxic dose of 0.5 µmol/l gemcitabine             suppresses ADAM15 expression leading, at the same time, to an increase in MICB             expression and a decrease in sMICB production in PANC-1 cells. The mRNA levels             of MICB did not change following PANC-1 exposure to gemcitabine. Further study             suggests that the suppressive effect of gemcitabine on MICB shedding in PANC-1             cells is mediated by ADAM15 downregulation. In conclusion, the results of the             present study support the hypothesis that ADAM15 is involved in MICB shedding             of PANC-1 cells and that gemcitabine inhibits MICB ectodomain shedding through             the suppression of ADAM15.
authors: Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, and Central South University, Changsha 410005, PR China.
authors: Xiaohui
authors: X
authors: Duan
authors: Xianhai
authors: X
authors: Mao
authors: Weijia
authors: W
authors: Sun
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015395:Histocompatibility Antigens Class I; C098080:MICB antigen; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D051722:ADAM Proteins; C098660:ADAM15 protein, human; D000093542:Gemcitabine