NR APUM
AU Diarra-Mehrpour,M.; Arrabal,S.; Jalil,A.; Pinson,X.; Gaudin,C.; Pietu,G.; Pitaval,A.; Ripoche,H.; Eloit,M.; Dormont,D.; Chouaib,S.
TI Prion protein prevents human breast carcinoma cell line from tumor necrosis factor alpha-induced cell death
QU Cancer Research 2004 Jan 15; 64(2): 719-27
PT journal article
AB 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 (PrPc), 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 PrPc 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 PrPc 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.
MH Breast Neoplasms/*pathology; Cell Death/*drug effects; Cell Line, Tumor; DNA, Complementary/genetics; *Drug Resistance, Neoplasm; Enzymes/genetics; Female; Human; Oligonucleotide Array Sequence Analysis; PrPc Proteins/*pharmacology; Support, Non-U.S. Gov't; Transfection; Tumor Necrosis Factor/*toxicity
AD mehrpour@igr.fr; Laboratoire de Cytokines et Immunologie des Tumeurs Humaines, Institut National de la Sante et de la Recherche Medicale U-487, Institut Gustave Roussy Pavillon de Recherche 1 and Institut Federatif de Recherche, Villejuif, France. Unite Mixte de Recherche 1161 de Virologie Institut National de Recherche Agronomique Agence Francaise de Securite Sanitaire des Aliments Ecole National Veterinaire d'Alfort, Maisons Alfort, France. Commisariat a l'Energie Atomique, Service de Genomique Fonctionnelle, Evry, France. Unite Mixte de Recherche 8125 Centre National de la Recherche Scientifique, Institut Gustave Roussy Pavillon de Recherche 2, Villejuif, France. Commisariat a l'Energie Atomique, Service de Neurovirologie, Centre de Recherche du Service Sante des Armes, Ecole Pratique des Hautes Etudes, Institut Paris sud sur les Cytokines, Universite Paris XI, Fontenay-aux-Roses, France.
SP englisch
PO USA