Genes and polypeptides relating to breast cancers
The present application provides novel human genes A7322, whose expression is markedly elevated in breast cancer. The present application also provides human genes F3374 whose expression is markedly elevated in breast cancer. These genes and polypeptides encoded thereby can be used, for example, in the diagnosis of breast cancer, and as target molecules for developing drugs against breast cancer. The invention features methods of screening for modulators of the kinase activity of PBK/TOPK. The invention further provides methods of screening for agents to prevent or treat cancer, such as breast cancer.
1. A method of screening an agent that induces apoptosis of cells expressing TOPK comprising the steps of:
(a) contacting a polypeptide selected from the group consisting of:
(1) a polypeptide comprising the amino acid sequence of SEQ ID NO: 92; and
(2) a polypeptide comprising the amino acid sequence of positions 32 to 318 of SEQ ID NO: 92, and that has a biological activity equivalent to the polypeptide consisting of the amino acid sequence of SEQ ID NO: 92;
with a substrate phosphorylated by the polypeptide and an agent under a condition that allows phosphorylation of the substrate, wherein the substrate is histone H3 or a fragment thereof that comprises at least its phosphorylation site;
(b) detecting the phosphorylation level of the substrate;
(c) comparing the phosphorylation level of the substrate with the phosphorylation level of the polypeptide detected in the absence of the agent; and
(d) selecting the agent that reduced the phosphorylation level of the substrate as an agent that induces apoptosis of the cells.
2. A method of screening an agent that induces apoptosis of breast cancer cells comprising the steps of:
(a) contacting a polypeptide selected from the group consisting of:
(1) a polypeptide comprising the amino acid sequence of SEQ ID NO: 92; and
(2) a polypeptide comprising the amino acid sequence of positions 32 to 318 of SEQ ID NO: 92, and that has a biological activity equivalent to the polypeptide consisting of the amino acid sequence of SEQ ID NO: 92;
with a substrate phosphorylated by the polypeptide and an agent under a condition that allows phosphorylation of the substrate, wherein the substrate is histone H3 or a fragment thereof that comprises at least its phosphorylation site;
(b) detecting the phosphorylation level of the substrate;
(c) comparing the phosphorylation level of the substrate with the phosphorylation level of the substrate detected in the absence of the agent; and
(d) selecting the agent that reduced the phosphorylation level of the substrate as an agent that induces apoptosis of breast cancer cells.
3. The method according to claim 1 or 2 , wherein the phosphorylation site is Ser 10 of histone H3.
4. A method of screening an agent that inhibits kinase activity of TOPK comprising the steps of:
(a) contacting a polypeptide selected from the group consisting of:
(1) a polypeptide comprising the amino acid sequence of SEQ ID NO: 92; and
(2) a polypeptide comprising the amino acid sequence of positions 32 to 318 of SEQ ID NO: 92, and that has a biological activity equivalent to the polypeptide consisting of the amino acid sequence of SEQ ID NO: 92;
with a histone H3 or a fragment thereof that comprises at least its phosphorylated site as substrate and an agent,
(b) detecting the phosphorylated level of the substrate;
(c) comparing the phosphorylated level of the substrate with the phosphorylated level of the substrate detected in the absence of the agent; and
(d) selecting the agent that reduced the phosphorylated level of the substrate as an inhibitor.
5. The method according to claim 4 , wherein the phosphorylation site is Ser 10 of histone H3.
6. A method of screening an agent for preventing or treating breast cancer comprising the steps of:
(a) contacting a polypeptide selected from the group consisting of:
(1) a polypeptide comprising the amino acid sequence of SEQ ID NO: 92; and
(2) a polypeptide comprising the amino acid sequence of positions 32 to 318 of SEQ ID NO: 92, and that has a biological activity equivalent to the polypeptide consisting of the amino acid sequence of SEQ ID NO: 92;
with a substrate phosphorylated by the polypeptide and an agent under a condition that allows phosphorylation of the substrate, wherein the substrate is histone H3 or a fragment thereof that comprises at least its phosphorylation site;
(b) detecting the phosphorylation level of the substrate;
(c) comparing the phosphorylation level of the substrate with the phosphorylation level of the substrate detected in the absence of the agent; and
(d) selecting the agent that reduced the phosphorylation level of the substrate as an agent for treating or preventing breast cancer.
7. The method according to claim 6 , wherein the phosphorylation site is Ser 10 of histone H3.