Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development.
Tumour metastasis is the principal cause of death for cancer patients. We have identified the nm23 gene, for which RNA levels are reduced in tumour cells of high metastatic potential. In this report we identify the cytoplasmic and nuclear Nm23 protein, and show that it also is differentially expressed in metastatic tumour cells. We also find that the human Nm23 protein has sequence homology over the entire translated region with a recently described developmentally regulated protein in Drosophila, encoded by the abnormal wing discs (awd) gene. Mutations in awd cause abnormal tissue morphology and necrosis and widespread aberrant differentiation in Drosophila, analogous to changes in malignant progression. The metastatic state may therefore be determined by the loss of genes such as nm23/awd which normally regulate development.
Rosengard
A M
AM
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland 20892.
Krutzsch
H C
HC
Shearn
A
A
Biggs
J R
JR
Barker
E
E
Margulies
I M
IM
King
C R
CR
Liotta
L A
LA
Steeg
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007301:Insect Hormones; D008969:Molecular Sequence Data; D008970:Molecular Weight; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D029721:Drosophila Proteins; D007301:Insect Hormones; D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; C061642:awd protein, Drosophila; D020559:Monomeric GTP-Binding Proteins