BRM EXPRESSION AND RELATED DIAGNOSTICS
The present invention relates to methods and compounds for causing BRM re-expression in cells, such as cancer cells, that have lost BRM expression. In particular, the present invention relates to screening methods for identifying BRM expression-promoting compounds. The present invention also relates to methods of accessing cancer risk through the identification of polymorphisms in the BRM promoter.
1 . A method identifying a BRM-expression-promoting compound comprising;
a) providing;
i) a candidate compound;
ii) a gluccocorticoid receptor agonist;
iii) a reporter construct, wherein said reporter construct comprises a reporter gene under the control of a promoter; and
iv) cells exhibiting reduced BRM expression;
b) integrating said reporter construct into said cells,
c) contacting said cells with said a gluccocorticoid receptor agonist and said candidate compound; and
d) detecting the activity of the reporter expressed from said reporter gene.
2 . The method of claim 1 , wherein said reporter gene is a luciferase gene and said reporter is a luciferase.
3 . The method of claim 1 , wherein said reporter activity is detected thereby indicating that said candidate compound promotes the expression of BRM.
4 . The method of claim 3 , further indicating that said candidate compound is not an inactivator of BRM.
5 . The method of claim 1 , wherein no said reporter activity is detecting thereby indicating that said candidate compound does not promote the expression of BRM or is an inactivator of BRM.
6 . The method of claim 1 , wherein said candidate compound is part of a chemical library.
7 . The method of claim 1 , wherein said cells are cancer cells.
8 . The method of claim 7 , wherein said cancer cells are breast cancer cells or prostate cancer cells.
9 . The method of claim 1 , wherein said cells are selected from the group consisting of: SW13, H522, A427, and H23.
10 . The method of claim 1 , wherein said cells are SW13 cells.
11 . The method of claim 1 , wherein gluccocorticoid receptor agonist is selected from the group consisting of: hydrocortisone, prenisone (deltasone), predrisonlone (hydeltasol), cortisol (hydrocortisone), dexamethasone, triamcinolone, betamethasone, beclomethasone, methylprednisolone, fludrocortisone acetate, deoxycorticosterone acetate (DOCA), and aldosterone.
12 . The method of claim 1 , wherein said promoter is a glucocorticoid inducible promoter.
13 . A method comprising:
a) obtaining a biological sample from a subject; and
b) analyzing said biological sample for the presence of one or more polymorphisms in the BRM promoter region.
14 . The method of claim 13 , wherein said biological sample is blood.
15 . The method of claim 13 , wherein said subject is human.
16 . The method of claim 13 , wherein said polymorphisim is comprised of an insertion at position −1321 of the BRM promoter region.
17 . The method of claim 16 , wherein said insertion at position −1321 comprises the insertion of the sequence TTTTAA at position −1321 of the BRM promoter region.
18 . The method of claim 13 , wherein said polymorphisim is comprised of an insertion at position −741 in the BRM promoter region.
19 . The method of claim 18 , wherein said insertion at position −741 comprises the insertion of the sequence TATTTTT at position −741 of the BRM promoter region.
20 . The method of claim 13 , wherein said presence of one or more polymorphisms in the BRM promoter region indicates the lack of BRM expression in said subject.
21 . The method of claim 20 , wherein said lack of BRM expression indicates a risk of cancer in said subject.