Hormonally up-regulated, neu-tumor-associated kinase

Abstract

This invention relates generally to a novel serine/threonine protein kinase, specifically to hormonally up-regulated, neu-tumor-associated kinase (HUNK); and to the nucleotide sequence encoding it. The kinase is temporally expressed during postnatal mammary development in a spatially heterogeneous manner in certain subsets of cells, and overexpressed in a subset of primary breast cancers. The invention further relates to an analysis of a correlation between carcinogenesis and postnatal development, particularly mammary development, especially associated with parity; to methods of using the kinase, or gene encoding it, as markers, prognostic tools, screening tools and therapies, in vitro and in vivo, that are based upon that correlation; and to the regulation of pregnancy-induced changes in the mammary tissue that occur in response to estrogen and progesterone.

1 . A purified cancer-linked protein kinase, Hunk. 
     
     
         2 . The purified protein of  claim 1 , comprising the amino acid sequence set forth in SEQ ID No. 2 or in SEQ ID No. 17. 
     
     
         3 . A method of delivering the kinase of  claim 1  to a target cell, wherein the method comprises delivering to the target cell an effective amount of the kinase. 
     
     
         4 . A method of delivering a therapeutically effective amount of the kinase of  claim 1  to a target cell in a patient in need of such kinase, wherein the method comprises delivering to the patient a therapeutically effective amount of the kinase of  claim 1 . 
     
     
         5 . The method of  claim 3 , wherein the kinase acts as a marker of target cell activity. 
     
     
         6 . A method of delivering to a target cell an inhibitor of the kinase of  claim 1 , wherein the method comprises delivering to the target cell an effective amount of the inhibitor to block the activation of, or decrease the activity of the kinase in the target cell. 
     
     
         7 . A method of delivering to a target cell an inhibitor of the kinase of  claim 1 , wherein the method comprises delivering to the target cell an effective amount of an antisense or anti-Hunk molecule to block the activation of, or decrease expression of, the kinase in the target cell. 
     
     
         8 . The method of  claim 6 , wherein the kinase is overexpressed or underexpressed in the target cell, as compared with a comparable normal cell. 
     
     
         9 . A method of delivering to a target cell an enhancer of the kinase of  claim 1 , wherein the method comprises delivering to the target cell an effective amount of a composition to activate or increase the activity of the kinase in the target cell. 
     
     
         10 . A method of treating cancer, hyperproliferative disease or oncogene expression in a patient, wherein the method comprises delivering to a target cell in the patient a therapeutically effective amount of the kinase of  claim 1 . 
     
     
         11 . A method of treating cancer, hyperproliferative disease or oncogene expression in a patient, wherein the method comprises delivering to a target cell in the patient a therapeutically effective amount of an inhibitor of the kinase of  claim 1  to block the activation of, or decrease the activity of, the kinase in the target cell. 
     
     
         12 . A method of treating cancer, hyperproliferative disease or oncogene expression in a patient, wherein the method comprises delivering to a target cell in the patient a therapeutically effective amount of an inhibitor of the kinase of  claim 1 , wherein the inhibitor comprises an antisense or anti-Hunk molecule. 
     
     
         13 . The method of  claim 10 , wherein the kinase is overexpressed or underexpressed in the target cell, as compared with a comparable normal cell. 
     
     
         14 . A method of treating cancer, hyperproliferative disease or oncogene expression in a patient, wherein the method comprises delivering to a target cell in the patient a therapeutically effective amount of an enhancer of the kinase of  claim 1 , wherein the method comprises delivering to the target cell an effective amount of a composition to activate or increase the activity of the kinase in the target cell. 
     
     
         15 . A method of diagnosing a cancer, carcinoma, sarcoma, neoplasm, leukemia, lymphoma or hyperproliferative cell disease or oncogene expression in a patient, wherein the method comprises detecting or measuring the kinase of  claim 1 , or detecting or measuring overexpression or underexpression of the kinase in a target cell, as compared with a comparable normal cell. 
     
     
         16 . A method of rapid screening for a selected compound that modulates activity of the kinase of  claim 1 , comprising: quantifying expression of the kinase from a target cell; treating the target cell by administering thereto the selected compound, wherein all other conditions are constant with those in the quantifying step; quantifying expression of the kinase from the treated target cell; and comparing the two quantification measurements to determine modulation of kinase activity achieved by treatment with the selected compound. 
     
     
         17 . The method of  claim 16 , wherein the modulated activity comprises an activation of the kinase, or an overexpression or a measurable increase in kinase activity, or an inactivation of the kinase, or an underexpression or a measurable decrease in kinase activity. 
     
     
         18 . The method of  claim 16 , wherein the modulated activity comprises transformation of the target cell. 
     
     
         19 . The method of  claim 16 , wherein the compound comprises one or more compositions. 
     
     
         20 . A method of using the kinase of  claim 1  as a prognostic tool in a patient, wherein the method comprises detecting the presence of the kinase or measuring activity of the kinase or a change in activity of the kinase as a molecular marker in the patient to predict behavior of a tumor, cancer, carcinoma, sarcoma, neoplasm, leukemia, lymphoma or hyperproliferative cell disease or oncogene expression in the patient, and applying that detection to predict the appropriate therapy for the patient to treat the tumor, cancer, carcinoma, sarcoma, neoplasm, leukemia, lymphoma or hyperproliferative cell disease or oncogene expression. 
     
     
         21 . An antibody specific for the polypeptide of  claim 1 , or for a homolog, analog, derivative or fragment thereof having Hunk activity.