Transcripts of the mitochondrial gene ND5 are overexpressed in highly metastatic murine large cell lymphoma cells.
The relative levels of mitochondrial specific gene transcripts were compared in two murine large cell lymphoma cell lines that differ in their propensities to form liver metastases and in their sensitivity to macrophage mediated antitumor cytostasis and cytolysis. Full-length transcripts of the mitochondrial genes were hybridized on electroblots from citrate/urea gels with specific gene prodes. The mitochondrially encoded gene NADH dehydrogenase subunit 5 (ND5), that encodes a component of NADH dehydrogenase (complex I) of the electron transport chain, was significantly overexpressed in the highly metastatic RAW117-H10 compared to low metastatic RAW117-P cells. Results from analysis of RNA blots were confirmed in an S1 nuclease protection assay. Since RAW117-H10 cells are significantly more resistant to cytostasis by activated macrophages in coculture and such macrophage activity can inhibit RAW117 tumor cell respiration and growth, a mechanism was suggested that allows RAW117 cell escape from certain host effector mechanisms that block cellular respiration by an increase in the in vivo concentrations of translatable messenger RNA (mRNA) that codes for key components of the electron transport chain.
LaBiche
R A
RA
Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Demars
M
M
Nicolson
G L
GL
D000818:Animals; D002460:Cell Line; D015342:DNA Probes; D004272:DNA, Mitochondrial / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D046911:Macromolecular Substances; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm; D046911:Macromolecular Substances; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011061:Poly A; D012313:RNA; D009245:NADH Dehydrogenase