Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis

被引:0
|
作者
Sophie Liot
Naïma El Kholti
Jonathan Balas
Laurent Genestier
Bernard Verrier
Ulrich Valcourt
Elise Lambert
机构
[1] Université Claude Bernard Lyon 1,Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique (LBTI), UMR CNRS 5305
[2] Institut de Biologie et Chimie Des Protéines,UR LIB « Lymphoma Immuno
[3] Université Claude Bernard Lyon I,Biology”
来源
Scientific Reports | / 11卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Pancreatic Ductal AdenoCarcinoma (PDAC) represents about 90% of pancreatic cancers. It is one of the most aggressive cancer, with a 5-year survival rate below 10% due to late diagnosis and poor therapeutic efficiency. This bad prognosis thus encourages intense research in order to better understand PDAC pathogenesis and molecular basis leading to the development of innovative therapeutic strategies. This research frequently involves the KC (LSL:KrasG12D;Pdx1-CRE) genetically engineered mouse model, which leads to pancreatic cancer predisposition. However, as frequently encountered in animal models, the KC mouse model also exhibits biases. Herein, we report a new adverse effect of KrasG12D mutation in KC mouse model. In our hands, 10% of KC mice developed clinical signs reaching pre-defined end-points between 100- and 150-days post-parturition, and associated with large thymic mass development. Histological and genetic analyses of this massive thymus enabled us (1) to characterize it as a highly proliferative thymic lymphoma and (2) to detect the unexpected recombination of the Lox-STOP-Lox cassette upstream KrasG12D allele and subsequent KRASG12D protein expression in all cells composing thymic masses. Finally, we highlighted that development of such thymic tumor was associated with accelerated pancreatic carcinogenesis, immune compartment disorganization, and in some cases, lung malignancies.
引用
收藏
相关论文
共 50 条
  • [1] Development of thymic tumor in [LSL:KrasG12D; Pdx1-CRE] mice, an adverse effect associated with accelerated pancreatic carcinogenesis
    Liot, Sophie
    El Kholti, Naima
    Balas, Jonathan
    Genestier, Laurent
    Verrier, Bernard
    Valcourt, Ulrich
    Lambert, Elise
    SCIENTIFIC REPORTS, 2021, 11 (01)
  • [2] Blockade of the CCK Receptor Inhibits Progression of Early PanIN Lesions to Pancreatic Cancer in the Pdx1-Cre, LSL/KrasG12D Mouse
    Matters, G.
    Cooper, T.
    Gilius, E.
    McGovern, C.
    Liao, J.
    Smith, J. P.
    PANCREAS, 2012, 41 (08) : 1384 - 1384
  • [3] Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice
    Bai, Han
    Li, Haonan
    Zhang, Wanying
    Matkowskyj, Kristina A.
    Liao, Jie
    Srivastava, Sanjay K.
    Yang, Guang-Yu
    CARCINOGENESIS, 2011, 32 (11) : 1689 - 1696
  • [4] Atorvastatin inhibits pancreatic carcinogenesis and increases survival in LSL-KrasG12D-LSL-Trp53R172H-Pdx1-Cre mice
    Liao, Jie
    Chung, Yeon T.
    Yang, Allison L.
    Zhang, Meng
    Li, Haonan
    Zhang, Wanying
    Yan, Liang
    Yang, Guang-Yu
    MOLECULAR CARCINOGENESIS, 2013, 52 (09) : 739 - 750
  • [5] Ethanol exposure of human pancreatic normal ductal epithelial cells induces EMT phenotype and enhances pancreatic cancer development in KC (Pdx1-Cre and LSL-KrasG12D) mice
    Yu, Wei
    Ma, Yuming
    Roy, Sanjit K.
    Srivastava, Rashmi
    Shankar, Sharmila
    Srivastava, Rakesh K.
    JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2022, 26 (02) : 399 - 409
  • [6] Changes in microRNA (miRNA) expression during pancreatic cancer development and progression in a genetically engineered KrasG12D;Pdx1-Cre mouse (KC) model
    Rachagani, Satyanarayana
    Macha, Muzafar A.
    Menning, Melanie S.
    Dey, Parama
    Pai, Priya
    Smith, Lynette M.
    Mo, Yin-Yuan
    Batra, Surinder K.
    ONCOTARGET, 2015, 6 (37) : 40295 - 40309
  • [7] Pdx1 expression in hematopoietic cells activates Kras-mutation to drive leukemia in KC (Pdx1-Cre; LSL-KrasG12D/+) mice
    Walcheck, Morgan T.
    Nukaya, Manabu
    Ranheim, Erik A.
    Matkowskyj, Kristina A.
    Ronnekleiv-Kelly, Sean
    LEUKEMIA & LYMPHOMA, 2023, 64 (06) : 1112 - 1122
  • [8] SEQUESTRATION OF OXIDIZED LIPIDS, IMMUNOMODULATION, AND TUMOR PROGRESSION IN PDX1-CRE;KRASG12D/+; P53FL/+ MOUSE MODEL
    McCaw, T.
    Klug, C.
    JOURNAL OF INVESTIGATIVE MEDICINE, 2014, 62 (04) : 716 - 716
  • [9] Increased CD3(+) cell infiltration during pancreatic intraepithelial neoplasia progression in KrasG12D/Pdx1-Cre transgenic mouse model
    Hong, Xiafei
    Dai, Hongmei
    Wang, Xianze
    Tian, Feng
    Wu, Wenming
    Zhao, Yupei
    CANCER IMMUNOLOGY RESEARCH, 2016, 4 (11)
  • [10] COX-2 inhibition reduces pancreatic intraductal neoplasia in Pdx-Cre/LSL-KRasG12D mice
    Thomas, R. M.
    Stuart, W. D.
    Boivin, G.
    Du, B.
    Subbaramaiah, K.
    Dannenberg, A. J.
    Lowy, A. M.
    ANNALS OF SURGICAL ONCOLOGY, 2007, 14 (02) : 15 - 15