ARIKUNI Hisashi Japanese Foundation for Cancer Research, Division of Molecular Pharmacology, Cancer Chemotherapy Center, Director of Institute, 横浜研究所, 所長(研究職)
DAN Shingo Japanese Foundation for Cancer Research, Division of Molecular Pharmacology, Cancer Chemotherapy Center, Member and Chief, Associate, 癌化学療法センター・分子薬理部, 研究員 (70332202)
|Budget Amount *help
¥11,900,000 (Direct Cost : ¥11,900,000)
Fiscal Year 2003 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 2002 : ¥6,500,000 (Direct Cost : ¥6,500,000)
Discovery of new biomarkers for diagnosis and therapy of cancer is important We previously established a "cancer cell lines panel" consisting of 39 human cancer cell lines derived from 8 different organ types, such as lung, stomach, colon, breast and so on. We have investigated their drug sensitivities and gene expression profiles and integrated all the data into a database, from which we have been getting various unique information on the molecular pharmacology of cancer. In the present study, we investigated the protein expression profiles of the 39 cancer cell lines by SELDI Proteinchip System (Ciphergen) and analyzed new biomarkers. Followings are the summary of the results.
1.We found that a 11970 Da protein was expressed exclusively in colon cancer cell lines, and identified it as prothymosin α (PT-α). It is an acidic nuclear protein and suggested to be involved in apoptosis. However, its function is not known well.
2.We prepared anti PT a antibodies and immunohistochemically exami
ned human colon cancer tissue. Then, adenoma expressed PT-α at a higher level than normal mucosa, and colon cancer tissue expressed it at an even higher level than adenoma This is the first observation indicating that PT-α is a new candidate of tumor marker. On the basis of this finding, we would like to validate PT α as a tumor marker by examining the larger number of colon cancer patients for its expression in the cancer tissue and in the blood. We also would like to analyze its function in colon cancer to examine whether it could be a molecular target of therapy.
3.To discover biomarkers for chemosensitiyity, we analyzed what alteration of protein expression profile occurs in cancer cells when exposed to anticancer drugs. NCI-H226 human lung cancer cells were exposed to 9 drugs, such as paclitaxel, cisplatin, and SN-38. Among various alterations, we recognized several proteins whose changes in the expression level were drug specific, which are the candidates of the biomarker for chemosensitivity. On he basis of this finding, we would like to extend our study to the identification and functional analysis of the candidate proteins and their validation.
Therefore, the protein chip analysis using the cancer cell lines panel is a useful methodology for discovering biomarkers, such as tumor marker and chemosensitivity markers. We would like to exploit it for development of diagnosis and therapy of cancer. Less