Suppression of the novel growth inhibitor p33ING1 promotes neoplastic transformation.
Using a new strategy for tumour suppressor gene isolation based on subtractive hybridization and the subsequent selection of transforming 'genetic suppressor elements', we have cloned a novel gene called ING1 encoding a 33-kD protein (p33ING1) that displays characteristics of a tumour suppressor. Acute expression of transfected constructs encoding this gene inhibited cell growth while chronic expression of ING1 antisense constructs promoted cell transformation. Limited analyses of tumour cell lines show that mutation of the ING1 gene occurs in neuroblastoma cells and reduced expression was seen in some breast cancer cell lines. These results demonstrate that ING1 can act as a potent growth regulator in normal and in established cells and provide evidence for a role as a candidate tumour suppressor gene whose inactivation may contribute to the development of cancers.
Garkavtsev
I
I
Department of Medical Biochemistry, University of Calgary, Alberta, Canada.
Kazarov
A
A
Gudkov
A
A
Riabowol
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C501503:ING1 protein, human; C501505:Ing1 protein, mouse; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins