Major research fields
Cell Growth Control, Cancer Research
Cancer is the most frequent cause of death in human. To conquer cancer, it is necessary to know how cancer occurs and how cancer cells differ from normal cells. We are analyzing molecular mechanism of carcinogenesis to elucidate what is specific to cancer cells and are seeking the way to specifically kill cancer cells. The primary feature of cancer cells is to grow out of control. The major players in cell growth control are the tumor suppressor pRB and the transcription factor E2F. E2F plays central roles in cell proliferation by activating growth-related genes. pRB suppresses carcinogenesis by suppressing E2F activity, thereby restraining cell proliferation. We found that, when the function of pRB is disabled by oncogenic changes, E2F is deregulated from pRB and specifically activates several tumor suppressor genes, thereby suppressing carcinogenesis. Importantly, these tumor suppressor genes are not activated by growth stimulation, which physiologically inactivates pRB. Moreover, the deregulated E2F activity, which activates the tumor suppressor genes, seems to specifically exist in cancer cells. Thus, the deregulated E2F may be a useful means to discriminate cancer cells from normal cells. We are trying to elucidate the function of and molecular nature of the deregulated E2F. We are also analyzing the molecular mechanism of oncogenesis induced by human T- cell leukemia virus type I (HTLV-I)
Major relevant publications
- Kitamura H, Ozono E, Iwanaga R, Bradford AP, Okuno J, Shimizu E, Kurayoshi K, Kugawa K, Toh H, Ohtani K.: Identification of novel target genes specifically activated by deregulated E2F in human normal fibroblasts. Genes Cells. 2015 in press
- Kurayoshi K, Ozono E, Iwanaga R, Bradford AP, Komori H, Ohtani K.: Cancer cell specific cytotoxic gene expression mediated by ARF tumor suppressor promoter constructs. Biochem Biophys Res Commun, 450, 240-246, 2014.
- Ozono E, Komori H, Iwanaga R, Tanaka T, Sakae T, Kitamura H, Yamaoka S, Ohtani K.: Tumor suppressor TAp73 gene specifically responds to deregulated E2F activity in human normal fibroblasts. Genes Cells, 17, 660-672, 2012.
- Iwanaga, R., Komori, H., Ishida, S., Okamura, N., Nakayama, K., Nakayama, K-I. and Ohtani, K.: Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners. Oncogene, 25, 1786-1798, 2006.
- 5. Komori, H., Enomoto, M., Nakamura, M., Iwanaga, R., and Ohtani, K.: Distinct E2F-mediated transcriptional program regulates p14ARF gene expression. EMBO J., 24, 3724-3736, 2005.