AIB1, a novel steroid receptor co-activator
AssigneesThe Government of the United States of America as represented by the Secretary of the, Department of Health and Human Services
InventorsPaul Meltzer, Jeffrey Trent
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Abstract
The invention features a substantially pure DNA which includes a sequence encoding a novel steroid receptor co-activator which is overexpressed in breast cancer cells, diagnostic assays for steroid hormone-responsive cancers, and screening assays to identify compounds which inhibit an interaction of the co-activator with the steroid hormone.
Claims24
A method of screening a candidate compound which inhibits an interaction of an AIB1 polypeptide with an ER polypeptide in a cell comprising
- (a) providing a GAL4 binding site linked to a reporter gene;
- (b) providing a GAL4 binding domain linked to either (i) an AIB1 polypeptide or (ii) an ER polypeptide;
- (c) providing a GAL4 transactivation domain II linked to the ER polypeptide if the GAL4 binding domain is linked to the AIB1 polypeptide or linked to the AIB1 polypeptide if the GAL4 binding domain is linked to the ER polypeptide;
- (d) contacting the cell with the compound;
- and
- (e) monitoring expression of the reporter gene, wherein a decrease in expression in the presence of the compound compared to that in the absence of the compound indicates that the compound inhibits an interaction of an AIB1 polypeptide with the ER polypeptide.
A method of detecting an aberrantly proliferating cell in a tissue sample comprising determining the level of AIB1 gene expression in the sample, wherein an increase in the level of expression compared to the level in normal control tissue indicates the presence of an aberrantly proliferating cell.
A method of detecting breast cancer in a tissue sample, comprising determining the number of cellular copies of an AIB1 gene in the tissue sample, wherein an increase in the number of copies compared to the number of copies in a normal control tissue indicates the presence of a breast carcinoma.
A method of reducing proliferation of a cancer cell in a mammal comprising administering to the mammal a compound which inhibits expression of AIB1.
A method of inhibiting ER-dependent transcription in a breast cell of an mammal, comprising administering an effective amount of an AIB1 polypeptide to the mammal.
A method of identifying a tamoxifen-sensitive patient, comprising
- (a) contacting a patient-derived tissue sample with tamoxifen;
- and
- (b) determining the level of AIB1 gene expression in the sample, wherein an increase in the level of expression compared to the level in normal control tissue indicates that the patient is tamoxifen-sensitive.
A method of reducing proliferation of a cancer cell comprising administering to the mammal a compound which inhibits interaction of AIB1 with a molecule selected from the group consisting of steroid receptors and nuclear co-factors.
Dependencies are inferred from the claim text.