title: Prion protein prevents human breast carcinoma cell line from tumor necrosis factor alpha-induced cell death.
abstract: To define genetic determinants of tumor cell resistance to the cytotoxic action of tumor necrosis factor alpha (TNF), we have applied cDNA microarrays to a human breast carcinoma TNF-sensitive MCF7 cell line and its established TNF-resistant clone. Of a total of 5760 samples of cDNA examined, 3.6% were found to be differentially expressed in TNF-resistant 1001 cells as compared with TNF-sensitive MCF7 cells. On the basis of available literature data, the striking finding is the association of some differentially expressed genes involved in the phosphatidylinositol-3-kinase/Akt signaling pathway. More notably, we found that the PRNP gene coding for the cellular prion protein (PrP(c)), was 17-fold overexpressed in the 1001 cell line as compared with the MCF7 cell line. This differential expression was confirmed at the cell surface by immunostaining that indicated that PrP(c) is overexpressed at both mRNA and protein levels in the TNF-resistant derivative. Using recombinant adenoviruses expressing the human PrP(c,) our data demonstrate that PrP(c) overexpression converted TNF-sensitive MCF7 cells into TNF-resistant cells, at least in part, by a mechanism involving alteration of cytochrome c release from mitochondria and nuclear condensation.
authors.affiliation: Laboratoire de Cytokines et Immunologie des Tumeurs Humaines, Institut National de la Santé et de la Recherche Médicale U-487, Institut Gustave Roussy Pavillon de Recherche 1 and Institut Fédératif de Recherche, Villejuif, France. mehrpour@igr.fr
authors.forename: Maryam
authors.initials: M
authors.lastname: Diarra-Mehrpour
authors.forename: Samuel
authors.initials: S
authors.lastname: Arrabal
authors.forename: Abdelali
authors.initials: A
authors.lastname: Jalil
authors.forename: Xavier
authors.initials: X
authors.lastname: Pinson
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaudin
authors.forename: Geneviève
authors.initials: G
authors.lastname: Piétu
authors.forename: Amandine
authors.initials: A
authors.lastname: Pitaval
authors.forename: Hugues
authors.initials: H
authors.lastname: Ripoche
authors.forename: Marc
authors.initials: M
authors.lastname: Eloit
authors.forename: Dominique
authors.initials: D
authors.lastname: Dormont
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D004798:Enzymes / Q000235:genetics; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D018621:PrPC Proteins / Q000494:pharmacology*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
chemical_list: D018076:DNA, Complementary; D004798:Enzymes; D018621:PrPC Proteins; D014409:Tumor Necrosis Factor-alpha