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Proteomic characterization of EL4 lymphoma‐derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase‐6 during tumor cell death in vivo
Author(s) -
Kramer David A.,
Eldeeb Mohamed A.,
Wuest Melinda,
Mercer John,
Fahlman Richard P.
Publication year - 2017
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201700060
Subject(s) - downregulation and upregulation , in vivo , etoposide , biology , cancer research , programmed cell death , apoptosis , lymphoma , chemotherapy , immunology , biochemistry , genetics , microbiology and biotechnology , gene
The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in‐depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo . Using a label‐free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase‐3 and an upregulation of caspase‐6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor.