Use Of A Growth-Stimulating Protein

Abstract

This invention relates to the inhibition of a newly discovered growth-stimulating protein in an individual. Further, the invention relates to a method for preventing or treating a cancer, or preventing or treating cancer growth, invasion or metastasis, or preventing or treating other hyperproliferative diseases in an individual, by down regulating the expression of said growth-stimulating protein or by inactivating said protein. Still further, the invention concerns a method for diagnosing cancer or other hyperproliferative diseases in an individual based on said growth-stimulating protein.

1 . A method for screening and identifying a therapeutic agent, which inhibits KIAA1524, said method comprising the steps of:
 a) providing a first protein immobilized in a reaction chamber,   b) adding a candidate agent and a labeled second protein to said chamber concomitantly or subsequently in any order,   c) determining whether said first protein binds to said second protein, and   d) identifying said candidate agent as a therapeutic agent inhibiting KIAA1524 when the determination in step c) is negative,   wherein said first protein is KIAA1524 and said second protein is selected from the group consisting of PP2A, subunits thereof, and c-Myc, or vice versa.   
     
     
         2 . The method according to  claim 1 , wherein said second protein is labeled with a label selected from the group consisting of fluorescent labels, luminescent labels and calorimetric labels. 
     
     
         3 . The method according to  claim 1 , wherein step c) is performed by a plate reader. 
     
     
         4 . Small interfering RNA comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:s 2 to 6, and inhibiting KIAA1524. 
     
     
         5 . A peptide comprising at least one amino acid sequence selected from the group consisting of SEQ ID NO:s 7 to 30, 32 to 79, and conservative sequence variants thereof, and inhibiting KIAA1524. 
     
     
         6 . The peptide according to  claim 5 , wherein said peptide comprises 1 to 20 consecutive sequences selected from the group consisting of SEQ ID NO:s 32 to 79 and conservative sequence variants thereof. 
     
     
         7 . The peptide according to  claim 5 , wherein said peptide comprises 1 to 20 consecutive sequences selected from the group consisting of SEQ ID NO:s 7 to 30 and conservative sequence variants thereof. 
     
     
         8 . A method for producing a pharmaceutical composition, said method comprising identifying an agent which inhibits KIAA1524 and mixing said agent with any suitable pharmaceutically acceptable excipient. 
     
     
         9 . The method according to  claim 8 , wherein said identification is performed by a method for screening and identifying a therapeutic agent which inhibits KIAA1524, said method comprising the steps:
 a) providing a first protein immobilized in a reaction chamber,   b) adding a candidate agent and a labeled second protein to said chamber concomitantly or subsequently in any order,   c) determining whether said first protein binds to said second protein, and   d) identifying said candidate agent as a therapeutic agent inhibiting KIAA1524 when the determination in step c) is negative,   wherein said first protein is KIAA1524 and said second protein is selected from the group consisting of PP2A, subunits thereof, and c-Myc, or vice versa.   
     
     
         10 . A pharmaceutical composition produced according to  claim 8 . 
     
     
         11 . A method of inhibiting KIAA1524 in a human or animal patient in need thereof by administering a therapeutically effective amount of a pharmaceutical composition according to  claim 10 . 
     
     
         12 . The method according to  claim 11 , wherein said patient suffers from a disease selected from the group consisting of cancer and other hyperproliferative diseases. 
     
     
         13 . The method according to  claim 12 , wherein said cancer is selected from the group consisting of squamous cell cancer of the head-and-neck region, breast cancer and colon cancer. 
     
     
         14 . The method according to  claim 12 , wherein said hyperproliferative disease is selected from the group consisting of psoriasis, myocardial hypertrophy and benign tumor. 
     
     
         15 . A method of treating and/or alleviating a disease selected from the group consisting of cancer and other hyperproliferative diseases, comprising the step of:
 administering a therapeutically effective amount of a pharmaceutical composition comprising an agent, which inhibits KIAA1524.   
     
     
         16 . The method according to  claim 15 , wherein said cancer is selected from the group consisting of squamous cell cancer of the head-and-neck region, breast cancer and colon cancer. 
     
     
         17 . The method according to  claim 15 , wherein said hyperproliferative disease is selected from the group consisting of psoriasis, myocardial hypertrophy and benign tumor. 
     
     
         18 . The method according to  claim 15  wherein the agent is an antisense oligonucleotide, a small interfering RNA (siRNA), or a ribozyme. 
     
     
         19 . The method according to  claim 18 , wherein said siRNA is selected from the group consisting of SEQ ID NO:s 2 to 6. 
     
     
         20 . The method according to  claim 15 , wherein the agent prevents or inhibits cell proliferation and growth by inhibiting said KIAA1524 protein from interacting with PP2A complex or with the transcription factor c-Myc, or wherein said agent inhibits KIAA1524 proliferative and growth effects that are not dependent on KIAA1524 interaction with PP2A or c-Myc. 
     
     
         21 . The method according to  claim 15 , wherein the agent is a peptide, a small molecule, an antibody or an aptamer. 
     
     
         22 . The method according to  claim 21 , wherein said peptide comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO:s 7 to 30, 32 to 79, and conservative sequence variants thereof. 
     
     
         23 . The method according to  claim 22 , wherein said peptide comprises 1 to 20 consecutive sequences selected from the group consisting of SEQ ID NO:s 32 to 79 and conservative sequence variants thereof. 
     
     
         24 . The method according to  claim 22 , wherein said peptide comprises 1 to 20 consecutive sequences selected from the group consisting of SEQ ID NO:s 7 to 30 and conservative sequence variants thereof. 
     
     
         25 . The method according to  claim 15  wherein the agent inactivates the KIAA1524 in the region ranging from aa 461 through 533 or any other region on KIAA1524 that participates on interaction between PP2A complex and KIAA1524 protein. 
     
     
         26 . A method for determining the invasiveness of a malignant change in a mammal suspected to suffer from cancer, said method comprising the steps of:
 a) assessing the level of KIAA1524 expression in a sample, suspected to comprise malignant cells, taken from said mammal,   b) comparing the expression level from step a) with the expression level of KIAA1524 in a non-malignant control sample, and   c) determining said malignant changes as invasive when the expression level of KIAA1524 in said sample is significantly higher than the expression level of KIAA1524 in a non-malignant control sample.   
     
     
         27 . The method according to  claim 26 , further comprising determining said malignant changes as gradus III or IV, when the expression level of KIAA1524 in said sample is more than 2 times higher than in a non-malignant control sample or in non-invasive gradus I and II samples. 
     
     
         28 . The method according to  claim 27 , wherein said cancer is colon cancer. 
     
     
         29 . The method according to  claim 26 , further comprising distinguishing invasive tumor types selected from the group consisting of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC) and IDC with intraductal comedo carcinoma (IDC+ICC), from non-invasive tumor types when the expression level of KIAA1524 in said sample is more than 2 times higher than in a non-malignant control sample. 
     
     
         30 . A pharmaceutical composition comprising a small interfering RNA according to  claim 4 . 
     
     
         31 . A method of inhibiting KIAA1524 in a human or animal patient in need thereof by administering a therapeutically effective amount of a pharmaceutical composition according to  claim 30 . 
     
     
         32 . The method according to  claim 31 , wherein said patient suffers from a disease selected from the group consisting of cancer and other hyperproliferative diseases. 
     
     
         33 . The method according to  claim 32 , wherein said cancer is selected from the group consisting of squamous cell cancer of the head-and-neck region, breast cancer and colon cancer. 
     
     
         34 . The method according to  claim 32 , wherein said hyperproliferative disease is selected from the group consisting of psoriasis, myocardial hypertrophy and benign tumor. 
     
     
         35 . A pharmaceutical composition comprising a peptide according to  claim 5 . 
     
     
         36 . A method of inhibiting KIAA1524 in a human or animal patient in need thereof by administering a therapeutically effective amount of a pharmaceutical composition according to  claim 35 . 
     
     
         37 . The method according to  claim 36 , wherein said patient suffers from a disease selected from the group consisting of cancer and other hyperproliferative diseases. 
     
     
         38 . The method according to  claim 37 , wherein said cancer is selected from the group consisting of squamous cell cancer of the head-and-neck region, breast cancer and colon cancer. 
     
     
         39 . The method according to  claim 37 , wherein said hyperproliferative disease is selected from the group consisting of psoriasis, myocardial hypertrophy and benign tumor.