Method for treating or preventing bladder cancer using the depdc1 polypeptide
AssigneeOncotherapy Science, Inc.
InventorsYusuke Nakamura, Toyomasa Katagiri, Akira Togashi
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Abstract
The present invention provides therapeutic agents and methods for treating cancer using the polypeptides posed of an amino acid sequence which includes a polypeptide fragment of DEPDC1. The polypeptides of the present invention can be introduced into cancer cells by modifying the polypeptides with transfection agents such as poly-arginine. Furthermore, the present invention provides methods of screening for therapeutic agents or compounds useful in inhibition of the DEPDC1/ZN-F224 complex formation or the treatment of cancer. The present invention also provides siRNAs targeting the ZNF224 gene, which are suggested to be useful in the treatment of bladder cancer.
Claims36
A polypeptide comprising an amino acid sequence of SEQ ID NO:
- 28 or a polypeptide functionally equivalent thereto, wherein the polypeptides lacks the biological function of a peptide consisting of SEQ ID NO:
- 45 or 47.
A method of screening for a candidate compound for treating or preventing a cancer associated with DEPDC1 or inhibiting the binding between DEPDC1 and ZNF224, said method comprising the steps of:
- (a) contacting a DEPDC1 polypeptide or functional equivalent thereof with a ZNF224 polypeptide or functional equivalent thereof, in the presence of a test compound;
- (b) detecting the binding between the polypeptides;
- and
- (c) selecting the test compound that inhibits the binding between these polypeptides.
A method of screening for a candidate compound for treating or preventing a cancer associated with DEPDC1 or inhibiting a DEPDC1- and ZNF224-expressing cancer cell growth, said method comprising the steps of:
- (a) contacting a candidate compound with a cell expressing DEPDC1 and ZNF224 and
- (b) selecting the candidate compound that increases the expression level of DLG1 or A20 (TNFAIP3) as compared with the expression level detected in the absence of the test compound.
A method of screening for a candidate compound for treating or preventing a cancer associated with DEPDC1 or inhibiting a DEPDC1-expressing cancer cell growth, said method comprising the steps of:
- (a) contacting a candidate compound with a cell expressing DEPDC1 and ZNF224 into which a vector, comprising the transcriptional regulatory region of DLG1 or A20 (TNFAIP3) and a reporter gene that is expressed under the control of the transcriptional regulatory region, has been introduced;
- (b) measuring the expression or activity of said reporter gene;
- and
- (c) selecting a candidate compound that increases the expression or activity level of said reporter gene as compared to a control.
A double-stranded molecule comprising a sense strand and an antisense strand, wherein the sense strand comprises a nucleotide sequence corresponding to a target sequence consisting of SEQ ID NO:
- 57 or 58, and wherein the antisense strand comprises a nucleotide sequence which is complementary to said sense strand, and wherein said double-stranded molecule, when introduced into a cell expressing the ZNF224 gene, inhibits expression of said gene.
A method of treating or preventing cancer in a subject comprising administering to said subject a pharmaceutically effective amount of a double-stranded molecule against a ZNF224 gene or a vector encoding said double-stranded molecule, and a pharmaceutically acceptable carrier, wherein the double-stranded molecule and the vector inhibits the cell proliferation contacting with the cell expressing ZNF224 gene.
A composition for treating or preventing cancer, which comprises a pharmaceutically effective amount of a double-stranded molecule against a ZNF224 gene or a vector comprising said double-stranded molecule, and a pharmaceutically acceptable carrier, wherein the double-stranded molecule and the vector inhibit the cell proliferation contacting with the cell expressing ZNF224 gene.
Dependencies are inferred from the claim text.