The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A meth
The present application provides methods of prevention and/or treatment of breast cancer in a subject by inhibiting expression of PAX2. In the cancer treatment methods disclosed, the method of inhibiting expression of PAX2 can be by administration of a nucleic acid encoding an siRNA for PAX2. A method of treating cancer in a subject by administering DEFB1 is also provided. Similarly, provided is a method of treating cancer in a subject by increasing expression of DEFB1 in the subject.
대표청구항▼
1. A method for treating a breast condition in a subject, comprising: (a) determining a PAX2-to-DEFB1 expression ratio in breast tissue from said subject;(b) determining an estrogen receptor/progesterone receptor (ER/PR) status of said breast tissue from said subject; and(c) based on the results of
1. A method for treating a breast condition in a subject, comprising: (a) determining a PAX2-to-DEFB1 expression ratio in breast tissue from said subject;(b) determining an estrogen receptor/progesterone receptor (ER/PR) status of said breast tissue from said subject; and(c) based on the results of (a) and (b), administering to a breast tissue of said subject, a composition that inhibits PAX2 expression or PAX2 activity,wherein said composition comprises one or more agents selected from the group consisting of a polynucleotide encoding an siRNA for PAX2, a polynucleotide that blocks binding of PAX2 to a DEFB1 promoter, an antagonist of angiotensin II, an antagonist of angiotensin II receptor, an antagonist of angiotensin-converting enzyme (ACE), an antagonist of mitogen-activated protein kinase (MEK), an antagonist of extracellular signal-regulated kinase 1,2 (ERK1,2), an antagonist of signal transducer and activator of transcription 3 (STAT3), and a blocker of the renin-angiotensin system (RAS) signaling pathway andwherein said composition that blocks the binding of PAX2 to the DEFB1 promoter comprises a polynucleotide comprising SEQ ID NO:1. 2. The method of claim 1, wherein said breast condition is breast cancer or MIN. 3. The method of claim 1, wherein said composition comprises a polynucleotide comprising SEQ ID NO:1 in forward or reverse orientation. 4. The method of claim 3, wherein said polynucleotide comprises the sequence of V-CCTTG-W, wherein each of V and W consist of a contiguous nucleotide sequence of 1 to 35 nucleotides that flank the CCTTG sequence of the DEFB1 promoter, and a complementary sequence thereof. 5. The method of claim 4, wherein said polynucleotide comprises a sequence selected from the group consisting of SEQ ID NOS: 16, 25 and 28. 6. The method of claim 1, wherein said composition is an anti-PAX2 agent conjugated to an antibody, a receptor or a ligand to target tumor tissue in said subject. 7. The method of claim 1, wherein step (c) further comprises administering a composition comprising an anti-hormonal agent. 8. The method of claim 7, wherein the anti-hormonal agent is Tamoxifen. 9. The method of claim 1, wherein step (c) further comprises administering a composition comprising an anti-ERBB-2/anti-Her-2 agent. 10. The method of claim 9, wherein the anti-ERBB-2/anti-Her-2 agent is Trastuzumab. 11. The method of claim 1, wherein step (c) further comprises administering a composition comprising an anti-AIB-1/SRC-3 agent. 12. The method of claim 1, wherein a compound that inhibits PAX2 expression or inhibits PAX2 activity is administered when the PAX2-to-DEFB1 expression ratio is elevated and the ER/PR status is ER+/PR+ or ER+/PR−. 13. A method for treating a breast condition in a subject, comprising administering to a breast tissue of the subject, a composition that inhibits PAX2 expression and/or PAX2 activity, wherein said composition comprises an anti-PAX2 siRNA.
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