Increased expression of nucleoside diphosphate kinase/nm23 and c-Ha-ras mRNA is associated with spontaneous lung metastasis in rat-transplantable osteosarcomas.
The relationship between expression of nucleoside diphosphate kinase (NDP kinase)/nm23, c-Ha-ras, and c-myc genes and metastatic potential was assessed in rat-transplantable osteosarcoma lines, derived from spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcomas in Fischer 344/NS1c rats. These osteosarcomas possess metastatic potential and highly metastatic lines spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions were respectively established by selectively transplanting lung metastatic lesions. Northern blot analysis revealed that the levels of NDP kinase/nm23 and c-Ha-ras gene expression were increased in line with metastatic ability; thus transcript levels were remarkably greater in both spontaneous osteosarcoma-selected lung metastatic lesions and 4-hydroxyamino-quinoline 1-oxide-induced osteosarcoma-selected lung metastatic lesions highly metastatic lines than in their respective low metastatic spontaneous and chemical carcinogen (4-hydroxyamino quinoline 1-oxide)-induced osteosarcoma counterparts. c-myc mRNA expression was observed in all tumor lines, without any correlation with metastatic ability. Southern blot analysis did not show evidence of gross rearrangement or amplification of NDP kinase/nm23, c-Ha-ras, or c-myc genes suggesting regulation of their gene expression at the transcriptional and/or posttranscriptional level. These results indicate that NDP kinase/nm23 and c-Ha-ras might be cooperatively involved in a positive manner in signal transduction processes, especially involving G-protein reactions, responsible for metastasis of rat-transplantable osteosarcomas.
Honoki
K
K
Department of Orthopedic Surgery, Nara Medical University, Japan.
Tsutsumi
M
M
Miyauchi
Y
Y
Mii
Y
Y
Tsujiuchi
T
T
Morishita
T
T
Miura
S
S
Aoki
M
M
Kobayashi
E
E
Tamai
S
S
D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D016259:Genes, myc; D011905:Genes, ras; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000201:enzymology; D009701:Nucleoside-Diphosphate Kinase / Q000096:biosynthesis*; D012516:Osteosarcoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D010179:Pancreas / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic
D017931:DNA Primers; D012333:RNA, Messenger; D009701:Nucleoside-Diphosphate Kinase