Method of detecting androgen-regulated gene

• US 20030170713A1
• Filed: 03/18/2003
• Published: 09/11/2003
• Est. Priority Date: 01/28/2000
• Status: Abandoned Application

• Current Assignee: Henry M Jackson Foundation For The Advancement of Military Medicine Incorporated
• Original Assignee: Henry M Jackson Foundation For The Advancement of Military Medicine Incorporated
• Inventors: Segawa, Takehiko, Srivastava, Shiv, Moul, Judd W., Xu, Linda L.
• Application Number:
  US10/390,045
• Publication Number:
  US 20030170713A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE

Abstract

This invention relates to androgen-regulated nucleic acids, a polynucleotide array containing these androgen-regulated nucleic acids, and methods of using the polynucleotide array in the diagnosis and prognosis of prostate cancer.

Claims

1. A polynucleotide array comprising:

(a) a planar, non-porous solid support having at least a first surface; and

(b) a first set of polynucleotide probes attached to the first surface of the solid support, wherein the first set of polynuceotide probes comprises polynucleotide sequences derived from genes that are up-regulated or down-regulated in response to androgen.

2. The polynucleotide array of claim 1, wherein the polynucleotide sequences are derived from the genes of LNCaP cells that are up-regulated or down-regulated in response to androgen.

3. The polynucleotide array of claim 2, wherein the androgen is R1881.

4. The polynucleotide array of claim 1, wherein the first set of polynuceotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 3.

5. The polynucleotide array according to claim 1, further comprising a second set of polynucleotide probes, wherein the second set of polynucleotide probes comprises polynucleotide sequences derived from genes that are involved in testosterone biosynthesis and metabolism.

6. The polynucleotide array according to claim 4, further comprising a second set of polynucleotide probes, wherein the second set of polynucleotide probes comprises polynucleotide sequences derived from genes whose expression is altered in prostate cancer or is specific to prostate tissue.

7. The polynucleotide array according to claim 6, wherein the second set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 6.

8. The polynucleotide array according to claim 1, further comprising a second set of polynucleotide probes, wherein the second set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 8.

9. The polynucleotide array according to claim 7, further comprising a third, fourth, fifth, and sixth set of polynucleotide probes, wherein the third set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 4, the fourth set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 5, the fifth set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 7, and the sixth set of polynucleotide probes comprises polynucleotide sequences derived from the polynucleotide sequences listed in Table 8.

10. The polynucleotide array of claim 1, wherein at least one of the genes that is up-regulated in response to androgen is the polynucleotide sequence of SEQ ID NO:

2.

11. The polynucleotide array of claim 1, wherein at least one of the polynucleotide sequences comprises the polynuleotide sequence of SEQ ID NO:

2

12. A method of identifying an expression profile of androgen-regulated genes in a target cell, comprising hybridizing the nucleic acids of the target cell with the polynucleotide array of claim 1 to obtain a hybridization pattern, wherein the hybridization pattern represents the expression profile of androgen-regulated genes in the target cell.

13. A method of identifying an expression profile of androgen-regulated genes in a target cell, comprising hybridizing the nucleic acids of the target cell with the polynucleotide array of claim 10 to obtain a hybridization pattern, wherein the hybridization pattern represents the expression profile of androgen-regulated genes in the target cell.

14. The method acording to claim 12, wherein the target cell is a prostate cell.

15. A method of diagnosing or prognosing prostate cancer, comprising

(a) hybridizing nucleic acids of a target cell of a patient with the polynucleotide array of claim 1 to obtain a first hybridization pattern, wherein the first hybridization pattern represents an expression profile of androgen-regulated genes in the target cell;

(b) comparing the first hybridization pattern of the target cell to a second hybridization pattern, wherein the second hybridization pattern represents an expression profile of androgen-regulated genes in prostate cancer, and

(c) diagnosing or prognosing prostate cancer in the patient.

16. A method of diagnosing or prognosing prostate cancer, comprising

(a) hybridizing nucleic acids of a target cell of a patient with the polynucleotide array of claim 10 to obtain a first hybridization pattern, wherein the first hybridization pattern represents an expression profile of androgen-regulated genes in the target cell;

(b) comparing the first hybridization pattern of the target cell to a second hybridization pattern, wherein the second hybridization pattern represents an expression profile of androgen-regulated genes in prostate cancer, and

(c) diagnosing or prognosing prostate caner in the patient.

17. The method acording to claim 15, wherein the target cell is a prostate cell.

18. An isolated nucleic acid molecule selected from:

(a) the polynucleotide sequence of SEQ ID NO;

2; and

(b) an isolated nucleic acid molecule that encodes a polypeptide having an amino acid sequence of SEQ ID NO;

3.

19. A recombinant vector that directs the expression of the nucleic acid molecule of claim 18.

20. A host cell transfected or transduced with the vector of claim 19.

21. The host cell of claim 20 selected from bacterial cells, yeast cells, and animal cells.

22. A method of detecting prostate cancer in a patient, comprising:

(a) detecting mRNA corresponding to the polynucleotide sequence of SEQ ID NO;

2 in a biological sample from the patient; and

(b) correlating the amount of mRNA corresponding to the polynucleotide sequence of SEQ ID NO;

2 in the sample with the presence of prostate cancer in the patient.

23. An isolated polypeptide, comprising the amino acid sequence of SEQ ID NO:

3.

24. An isolated antibody that binds to the polypeptide of claim 23.