Induction of apoptosis and cell growth inhibition by protein 4.33
AssigneeOregon Health & Science University
InventorsYoungman Oh, Ron Rosenfeld, Angela Renae Ingermann
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AssigneeOregon Health & Science University
InventorsYoungman Oh, Ron Rosenfeld, Angela Renae Ingermann
Estimating the term…
There is disclosed an isolated cDNA sequence (SEQ ID NO:1) encoding a P4.33 polypeptide and comprising a coding region (SEQ ID NO:2) of the sequence described in SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1. The P4.33 polypeptide functions as a specific cell-surface receptor for IGFBP-3, and undergoes nuclear translocation in combination with IGFBP-3. IGFBP-3 and P4.33 (IGFBP-3R) cooperatively suppress DNA synthesis and cell growth, and induce caspase activation and apoptosis in cancer cells, indicating that P4.33 is an important mediator of IGF-independent growth inhibitory actions of IGFBP-3. The P4.33:IGFBP-3 system of the present invention can be used, inter alia, in screening and diagnostic assays, and for therapeutic methods for cancer treatment and tumor suppression.
An isolated DNA sequence encoding a P4.33 protein or polypeptide and comprising a coding region of SEQ ID NO:1, or a sequence having at least 90% homology with the coding region of SEQ ID NO:1.
An isolated P4.33 protein or polypeptide expressed by the DNA sequence of SEQ ID NO:1, or expressed by a sequence having at least 90% homology with the coding region of SEQ ID NO:1.
A transfected cell comprising an expression vector having a DNA sequence that codes on expression for a P4.33 protein or polypeptide taken from the sequence of SEQ ID NO:2, or for a fusion protein comprising the P4.33 protein or polypeptide operatively associated with a heterologous polypeptide.
A method for identifying test compounds having therapeutic activity, comprising:
The method according to claim 0.5 wherein the P4.33 protein is present on a cell membrane or fragment thereof.
A method for identifying test compounds having therapeutic activity, comprising:
A method for identifying test compounds having therapeutic activity, comprising:
A method for identifying test compounds having therapeutic activity, comprising:
A method for treating or preventing cancer in a patient needing treatment, comprising administering to the patient in which such treatment or prevention is desired a therapeutically effective amount of an anti-P4.33 antibody that binds to the extracellular domain of P4.33.
A method for treating or preventing cancer in a patient needing treatment comprising administering to the patient in which such treatment or prevention is desired a therapeutically effective amount of a P4.33 antisense molecule, or ribozyme molecule.
An antibody specific for a P4.33 protein or peptide of SEQ ID NO:2, or for a fusion protein thereof.
An anticancer pharmaceutical composition comprising an antibody, or a binding fragment thereof, that binds to a P4.33 protein or peptide of SEQ ID NO:2, and a pharmaceutically acceptable carrier.
A method for targeting a therapeutic agent to solid tumor tissue, wherein the solid tumor tissue is characterized by expression of P4.33, comprising attaching the therapeutic agent to an isolated polypeptide, wherein the polypeptide binds to the extracellular domain of P4.33 at an affinity of at least 108.
An assay for cancer treatment, prognosis or diagnosis in a patient for cancer cells that express P4.33 protein or peptides, comprising:
An assay for cancer treatment, prognosis or diagnosis in a patient for cancer cells that express P4.33-specific sequences, comprising:
An antagonist of P4.33 biological activity, wherein the antagonist is a P4.33-specific antisense molecule, or a P4.33-specific ribozyme molecule.
An anticancer pharmaceutical composition comprising a therapeutically effective amount of a P4.33 antagonist, and a pharmaceutically acceptable carrier, wherein the P4.33 antagonist is a P4.33-specific antisense molecule, or a P4.33-specific ribozyme molecule.
An anticancer pharmaceutical composition comprising a therapeutically effective amount of a P4.33 protein or polypeptide of SEQ ID NO:2, and a pharmaceutically acceptable carrier.
An modulator of P4.33 biological activity, wherein the modulator is a polypeptide fragment comprising amino acids 88-264 of IGFBP-3.
Dependencies are inferred from the claim text.