title: Renal carcinoma cells undergo apoptosis without oligonucleosomal DNA fragmentation.
abstract: Apoptotic DNA fragmentation minimizes the risk of transferring genetic information from apoptotic cancer cells to the neighboring cells. We have reported previously that caspase-deficient human renal cell carcinoma (RCC) lines were almost completely resistant to apoptosis in response to cytotoxic agents. In the present report we examined apoptotic process in caspase competent RCC-91 cells. Apoptosis in RCC-91 cells was accompanied by activation of caspases-3 and -9; cleavage of PARP and DFF45 proteins; typical apoptotic nuclei fragmentation and mitochondrial collapse. Nevertheless, DNA in these cells was not degraded into oligonucleosomal fragments compared to control Jurkat cells. Expression of caspase-activated DNase, DFF40 accountable for characteristic ladder pattern was easily detectable in Jurkat but not renal cancer cells, providing one possible explanation for the lack of oligonucleosomal DNA fragmentation in apoptotic RCC cells. Lack of typical DNA fragmentation indicates a potential threat of transferring genetic information from one tumor cell to another or to the neighboring healthy cells.
authors.affiliation: Department of Urology, School of Medicine, Nihon University, Tokyo, Japan.
authors.forename: Kenya
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Robert
authors.initials: R
authors.lastname: Uzzo
authors.forename: Nickolai
authors.initials: N
authors.lastname: Dulin
authors.forename: James H
authors.initials: JH
authors.lastname: Finke
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kolenko
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000502:physiology*; D003851:Deoxyribonucleases / Q000096:biosynthesis; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D042541:Intracellular Space / Q000378:metabolism; D019169:Jurkat Cells; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009707:Nucleosomes / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009707:Nucleosomes; D000075223:Poly-ADP-Ribose Binding Proteins; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C109664:caspase-activated DNase inhibitor; C113696:DFFB protein, human; D003851:Deoxyribonucleases; D020169:Caspases