Pharmacogenomic analyzis of the responsiveness of gastrointestinal tumor cell lines to drug therapy: A transportome approach.
In this study, we have addressed the pharmacogenomic basis of the response of gastrointestinal tumors to six anticancer drugs using a panel of fifteen cell lines derived from pancreatic, stomach and biliary tract cancers. We determined the constitutive expression levels of 96 genes, whose encoded proteins contribute to drug action, and identified a major gene network that contains broad selectivity nucleoside transporter genes, as well as several genes known to be involved in cell proliferation and survival. All cell lines were exposed to 5'-DFUR, 5-FU, gemcitabine, cisplatin, doxorubicin and paclitaxel for 48h and cell response was measured using MTT assays. We correlated the cell response of the fifteen cell lines with the mRNA expression of the selected 96 genes and identified sets of 4-5 genes whose expression profiles correlated to responsiveness to each anticancer drug. These genes may be good candidates as response predictors to such therapies.
Molecular Pharmacology and Experimental Therapeutics (MPET), Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Spain; Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Natàlia
N
Grañé-Boladeras
Molecular Pharmacology and Experimental Therapeutics (MPET), Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Spain; Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Sandra
S
Pérez-Torras
Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Juan José
JJ
Lozano
Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Spain.
Marta R
MR
Romero
Molecular Pharmacology and Experimental Therapeutics (MPET), Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Spain; Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
Adela
A
Mazo
Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Spain.
José J G
JJG
Marín
Molecular Pharmacology and Experimental Therapeutics (MPET), Department of Biochemistry and Molecular Biology, Institute of Biomedicine (IBUB), University of Barcelona, Spain; Oncology Program, National Biomedical Research Institute on Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mpastor@ub.edu.
Marçal
M
Pastor-Anglada
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism
D000970:Antineoplastic Agents; D012333:RNA, Messenger
Digestive/gastrointestinal tumors; Network; Nucleoside analogs; Nucleoside transporters; Transportome