title: Methionine restriction induces apoptosis of prostate cancer cells via the c-Jun N-terminal kinase-mediated signaling pathway.
abstract: Tumors are relatively more sensitive to methionine restriction than corresponding normal tissues, a phenomenon known as methionine auxotrophy. The current studies were undertaken to elucidate the molecular mechanisms for methionine auxotrophy of prostate cancer cells. We found that the activity of c-Jun N-terminal kinase 1 (JNK1) increased dramatically in response to methionine restriction. Over expression of wild type JNK1 by transient transfection enhanced apoptosis in response to methionine restriction, whereas over expression of a kinase inactive mutant of JNK1 protected PC-3 human prostate cancer cells from apoptosis. We conclude that JNK1 plays a critical role in signaling cancer cells to undergo apoptosis in response to methionine restriction.
authors.affiliation: Department of Medicine, Baylor College of Medicine, and Houston VA Medical Center, Medical Service (111H), 2002 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Sara M
authors.initials: SM
authors.lastname: Hoestje
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Choo
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Epner
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D017209:Apoptosis; D015870:Gene Expression; D006367:HeLa Cells / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D008715:Methionine / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000473:pathology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D008715:Methionine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases