WO1998005797B1 - Prostate cancer drug screening - Google Patents
Prostate cancer drug screeningInfo
- Publication number
- WO1998005797B1 WO1998005797B1 PCT/US1997/013888 US9713888W WO9805797B1 WO 1998005797 B1 WO1998005797 B1 WO 1998005797B1 US 9713888 W US9713888 W US 9713888W WO 9805797 B1 WO9805797 B1 WO 9805797B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- enhancer
- cells
- gene
- expression
- psa
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Abstract
Screening of compounds for activity toward inhibition of prostate cancer cell proliferation is provided. A cell line is employed which can be used in conventional equipment for determining activity of compounds, where the cell line uses a marker whose expression is responsive to therapeutically active compounds.
Claims
[received by the International Bureau on 14 March 1998 (14.03.98); original claims 8-18 amended; new claims 19-25 added; remaining claims unchanged (3 pages)] combining said PSA expressing cells with a candidate drug in the presence of methyl trienolone or dihydrotestosterone for sufficient time for detectable expression of said enzyme; lysing said PSA expressing cells to provide a lysate and adding the substrate of said enzyme to said lysate; and detecting the level of expression of said enzyme as compared to the level of expression in the absence of said candidate drug.
7. A method according to Claim 6, wherein said PSA expressing cells are LNCaP cells and said enzyme is luciferase.
8. A method according to claims 1 or 6, wherein the prostate specific antigen enhancer comprises a sequence encompassing nucleotides between about -5824 to about - 3738 ofthe upstream region ofthe PSA gene, wherein the enhancer exhibits enhancer activity.
9. A method according to claims 1 or 6, wherein the prostate specific antigen enhancer is contained within a polynucleotide fragment of about 5.8 kilobases from about - 5824 to about +1 of the upstream region ofthe PSA gene, wherein the enhancer exhibits enhancer activity.
10. A method according to claim 10, wherein the promoter comprises a sequence encompassing nucleotides between about -560 to about +7 ofthe PSA gene.
11. A method for screening compounds for the treatment of prostate cancer employing cells comprising an expression construct, said expression construct comprising an enhancer of a prostate-specific gene and a promoter and a reporter gene whose expression product provides a detectable signal, wherein said reporter gene is under the transcriptional control of said enhancer, said method comprising the steps of: a) combining said cells with a candidate compound for a sufficient time for detectable expression of said reporter gene; and b) detecting the level of expression of said reporter gene as compared to the level of expression in the absence of said candidate compound.
33
12. A method according to claim 11, wherein said reporter gene expresses an enzyme.
13. A method according to claim 12, wherein said enzyme is luciferase.
14. A method according to claim 13, wherein said detecting comprises: lysing said cells; and assaying said lysate for luminescence.
15. A method according to claim 11, wherein said enhancer is an enhancer region ofthe human prostate specific antigen (PSA) gene.
16. A method according to claim 15, wherein the prostate specific antigen enhancer comprises a sequence encompassing nucleotides between about -5824 to about - 3738 ofthe upstream region of the PSA gene, wherein the enhancer exhibits enhancer activity.
17. A method according to claim 11, wherein said enhancer from the human glandular kallikrein (hKLK2) gene.
18. A method according to claim 17, wherein the hKLK2 enhancer comprises a sequence encompassing nucleotides about 1 to about 9765 of SEQ ID NO: l or active fragments thereof.
19. A method according to claim 17, wherein the hKLK2 enhancer comprises a sequence encompassing nucleotides about 5976 to about 9620 of SEQ ID NO: l or active fragments thereof.
20. A method according to claim 17, wherein the hKLK2 enhancer comprises a sequence encompassing nucleotides about 6859 to about 8627 of SEQ ID NO:l or active fragments thereof.
21. A method of any of claims 17 to 20, wherein the promoter is an hKLK2 promoter.
22. A method of any of claims 11 to 21, wherein the cells are mammalian.
34
23. A method of claim 22, wherein the mammalian cells express prostate specific antigen.
24. A method of claim 22 or 23, wherein the cells are prostate.
25. A method of claim 24, wherein the prostate cells contain an endogenous androgen receptor.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97937149A EP0918884A1 (en) | 1996-08-06 | 1997-08-06 | Prostate cancer drug screening |
| AU39729/97A AU3972997A (en) | 1996-08-06 | 1997-08-06 | Prostate cancer drug screening |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/692,759 | 1996-08-06 | ||
| US08/692,759 US5783435A (en) | 1996-08-06 | 1996-08-06 | Prostate cancer drug screenings |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO1998005797A1 WO1998005797A1 (en) | 1998-02-12 |
| WO1998005797B1 true WO1998005797B1 (en) | 1998-05-14 |
| WO1998005797A9 WO1998005797A9 (en) | 1998-07-09 |
Family
ID=24781904
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1997/013888 Ceased WO1998005797A1 (en) | 1996-08-06 | 1997-08-06 | Prostate cancer drug screening |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US5783435A (en) |
| AU (1) | AU3972997A (en) |
| WO (1) | WO1998005797A1 (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE376062T1 (en) | 1997-08-04 | 2007-11-15 | Cell Genesys Inc | ENHANCER OF HUMAN GLANDULAR KALLIC CLEANING, VECTORS CONTAINING IT AND METHODS OF ITS USE |
| WO1999041413A2 (en) * | 1998-02-12 | 1999-08-19 | Calydon, Inc. | Prostate cancer drug screening |
| AU5801699A (en) * | 1998-09-02 | 2000-03-21 | University Of Rochester | Prostate specific regulatory nucleic acid sequences |
| AU5723199A (en) * | 1998-09-15 | 2000-04-03 | Signalgene Inc. | Marker at the androgen receptor gene for determining breast cancer susceptibility |
| WO2000018961A2 (en) * | 1998-09-30 | 2000-04-06 | Millennium Pharmaceuticals, Inc. | Expression analysis of specific nucleic acids and polypeptides useful in the diagnosis and treatment of prostate cancer |
| US6872811B1 (en) | 1998-09-30 | 2005-03-29 | Millennium Pharmaceuticals, Inc. | HRPCa9 and HRPCa10 nucleic acids and polypeptides |
| US6495130B1 (en) | 1998-12-30 | 2002-12-17 | Calydon, Inc. | Target cell-specific adenoviral vectors containing E3 and methods of use thereof |
| EP1157126A4 (en) * | 1999-02-24 | 2005-03-02 | Gen Hospital Corp | PROCESS FOR CLONING INTERMEDIATE PRODUCTS FOR SIGNAL TRANSDUCTION |
| US7285414B2 (en) | 2000-09-26 | 2007-10-23 | Emory University | Viruses targeted to hypoxic cells and tissues |
| EP1328291B1 (en) * | 2000-09-26 | 2008-12-24 | Emory University | Viruses targeted to hypoxic cells and tissues |
| DE10061161A1 (en) * | 2000-11-30 | 2002-06-20 | Schering Ag | New human androgen receptor variants |
| JP2003018987A (en) * | 2001-06-25 | 2003-01-21 | Okazaki National Research Institutes | Transgenic cells and methods for detecting disruptors using the same |
| TW200418988A (en) * | 2002-09-30 | 2004-10-01 | Oncotherapy Science Inc | Method for diagnosing prostate cancer |
| CN1984925A (en) * | 2004-03-23 | 2007-06-20 | 肿瘤疗法科学股份有限公司 | Genes and polypeptides relating to prostate cancers |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2169466A1 (en) * | 1993-09-01 | 1995-03-09 | Peter Kushner | Methods for screening antiestrogen compounds |
| US5830686A (en) * | 1994-01-13 | 1998-11-03 | Calydon | Tissue-specific enhancer active in prostate |
| US5919652A (en) * | 1994-11-09 | 1999-07-06 | The Regents Of The University Of California | Nucleic acid molecules comprising the prostate specific antigen (PSA) promoter and uses thereof |
-
1996
- 1996-08-06 US US08/692,759 patent/US5783435A/en not_active Expired - Fee Related
-
1997
- 1997-08-06 WO PCT/US1997/013888 patent/WO1998005797A1/en not_active Ceased
- 1997-08-06 AU AU39729/97A patent/AU3972997A/en not_active Abandoned
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