ING-encoded p33ING1 protein as a mediator of p53 signaling pathway in mammalian cells
AssigneeBoard of Trustees for the University of Illinois
InventorsAndrei Gudkov, Igor Garkavstev, Karl Riabowol
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Abstract
The invention relates to a novel tumor suppressor gene, termed ING, genetic suppressor elements derived from this gene, and the protein produced by expression of this gene, known as p33ING1. The invention provides methods for characterizing mammalian cells on the basis of whether such cells express the ING gene, and embodiments of such methods directed at malignant or pre-malignant tissues in an animal for assaying the risk of developing malignant disease by the animal.
Claims23
An isolated nucleic acid encoding an amino acid sequence of a mammalian ING1 gene product identified by SEQ ID No. 7.
A homogeneous composition of a 26 kilodalton ING1 gene product having an amino acid sequence identified as SEQ ID No. 7.
A method of diagnosing a malignant or premalignant condition in a human, the method comprising the steps of:
- a) obtaining a cell or tissue sample from the human;
- b) assaying the sample to determine ING1 gene expression in the sample;
- c) comparing ING1 gene expression in the sample with ING1 gene expression in a nonmalignant human cells or tissue;
- wherein a malignant or premalignant condition is diagnosed when ING1 gene expression in the sample is less than ING1 gene expression in the nonmalignant human cells or tissues.
A method of screening a human sample to detect a malignant or premalignant condition, the method comprising the steps of:
- a) obtaining a cell or tissue sample from the human;
- b) assaying the sample to determine ING1 gene expression in the sample;
- c) comparing ING1 gene expression in the sample with ING1 gene expression in a nonmalignant human cells or tissue;
- wherein a malignant or premalignant condition is detected when ING1 gene expression in the sample is less than ING1 gene expression in the nonmalignant human cells or tissues.
A method of assessing a human sample to determine a risk of developing a malignant or premalignant condition, the method comprising the steps of:
- a) obtaining a cell or tissue sample from the human;
- b) assaying the sample to determine ING1 gene expression in the sample;
- c) comparing ING1 gene expression in the sample with ING1 gene expression in a nonmalignant human cells or tissue;
- wherein a risk for developing a malignant or premalignant condition is determined to exist when ING1 gene expression in the sample is less than ING1 gene expression in the nonmalignant human cells or tissues.
A genetic suppressor element encoding an antisense RNA having a nucleotide sequence identified as SEQ ID No. 1.
A method for activating p53-mediated transcription of a gene in a mammalian cell that expresses p53, the method comprising the step of introducing a recombinant expression construct encoding ING1 into the cell.
A diagnostic assay comprising the steps of
- (a) isolating cellular RNA comprising messenger RNA from a tumor or malignant cells from an animal;
- (b) measuring a level of expression of a ING1 gene in the tumor or malignant cells in the animal;
- (c) determining whether the level of expression of the ING1 gene in the tumor or malignant cells indicates that the ING1 gene is under-expressed in the tumor or malignant cells in the animal.
A diagnostic assay comprising the steps of
- (a) isolating cellular protein from a tumor or malignant cells from an animal;
- (b) measuring an amount of ING1 protein in the tumor or malignant cells in the animal;
- (c) determining whether the amount of ING1 protein in the tumor or malignant cells indicates that the ING1 protein is under-expressed in the tumor or malignant cells in the animal.
Dependencies are inferred from the claim text.