MASAAKI HAMAGUCHI


Masaaki Hamaguchi Associate Professor
Department of Biological Sciences Fordham University 441 East Fordham Road Bronx, NY 10458


hamaguchi@fordham.edu

The Hamaguchi Lab is at Fordham University. We are interested in genes responsible for cancer development. Our research projects include, genetic analysis of cancer cells, discovery of new cancer genes, and their characterization.

DBC2 and Breast Cancer

This page is intended to introduce our work on DBC2 and provide basic information about DBC2.

Breast Cancer
Breast cancer is the second leading cause of cancer death in women and by far the most common cancer. Understanding breast cancer at the genetic level will be helpful in overcoming this disease. If we could predict which individuals are at higher risk for breast cancer, certain preventive care can be provided. We may be able to develop methods to determine if treatment should be aggressive or conservative. Furthermore, better understanding of the causes of breast cancer will bring new insights into cancer development in general and therefore provide new ideas for prevention and treatment.

Tumor Suppressor Gene
Recent progress in molecular biology has brought us deeper understanding of cancer at the molecular level. Mutations of certain genes are now believed to play a critical role in cancer development. For example, genes called tumor suppressors prevent cells from growing out of control. They are frequently disabled in cancer cells, which then allows these cells to continue to grow and spread. Some tumor suppressor genes have been found in the familial form of breast cancer, but genes for the non-familial form of the disease remain unknown.

DBC2
We have discovered a new tumor suppressor gene, DBC2 (deleted in breast cancer 2), involved in breast cancer development. Our findings indicate this gene is disabled in more than half of breast cancer samples we examined. Furthermore, breast cancer cells stopped growing when DBC2 was reactivated in vitro. These results strongly support DBC2's role as a tumor suppressor.

Research Topics in Hamaguchi Lab
Human DBC2 - We discovered DBC2 and demonstrated that it suppresses breast cancer.
Mouse DBC2 - We cloned the mouse counterpart of DBC2.
Mutation Analysis - DBC2 was found to be mutated exclusively in cancer cells.
Expression Analysis - DBC2 is not functioning in breast cancer cells. (mechanisms unkown)
Computational Analysis - Structurally speaking, DBC2 belongs to previously uncharacterized RAS-BTB family.
Functional Analysis - Physiological function of DBC2 is unclear.
Knockout Mice - Animal models are not available yet.

Publication related to DBC2:
Hamaguchi, M., J. L. Meth, C. von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M. C. King, and M.H. Wigler. "DBC2, a candidate for a tumor suppressor gene involved in breast cancer." (2002) Proc. Natl. Acad. Sci. 99: pp.13647–13652. (PDF file, PNAS site)

Selected Publications

Tamari, M., Hamaguchi, M., Shmizu, M., Oshima, M., Takayama, H., Kohno, T., Yamaguchi, N., Sugimura, T., Terada, M. and Yokota, J. (1992): Ordering of Human Chromosome 3p Markers by Radiation Hybrid Mapping. Genomics 13: 705-712

Hamaguchi, M., Sakamoto, H., Tsuruta, H., Sasaki, H., Muto, T., Sugimura, T., and Terada, M. (1992): Establishment of a highly sensitive and specific exon-trapping system. Proc. Natl. Acad. Sci. USA. 89: 9779-9783.

Akiyama, N., Tsuruta, H., Sasaki, H., Sakamoto, H., Hamaguchi, M., Ohmura, Y, Seto, M., Ueda, R., Hirai, H., Yazaki, Y., Sugimura, T., and Terada, M. (1994): Messenger RNA levels of five genes located at chromosome 11q13 in B-cell tumors with chromosome translocation t(11;14)(q13;q32). Cancer Res. 54: 377-379.

Kohno, T., Otsuka, T., Takano, H., Yamamoto, T., Hamaguchi, M., Terada, M., and Yokota, J. (1995): Identification of a novel phospholipase C family gene at chromosome 2q33 that is homozygously deleted in human small cell lung carcinoma. Hum Mol Genet 4: 667-674.

Thiagalingam, S., Lisitsyn, N. A., Hamaguchi, M., Wigler, M. H., Willson, J. K., Markowitz, S. D., Leash, F. S., Kinzler, K. W., and Vogelstein, B. (1996): Evaluation of the FHIT gene in colorectal cancer. Cancer Res. 56: 2936-2939.

Hamaguchi, M., O’connor, B., Chen, T., McCombie, R., and Wigler, M. H. (1998): Rapid Isolation of cDNA by Hybridization Proc. Natl. Acad. Sci. USA. 95: 3764-3769.

Hamaguchi, M., Meth, J. L., Von Klitzing, C., Wei, W., Esposito, D., Rodgers, L., Walsh, T., Welcsh, P., King, M. C., Wigler, M. H. (2002): DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc. Natl. Acad. Sci. USA. 99: 13647-13652.

Siripurapu,V., Meth, J. L., Kobayashi, N., and Hamaguchi, M. (2005): DBC2 Significantly Influences Cell Cycle, Apoptosis, Cytoskeleton and Membrane Trafficking Pathways. J. Mol. Biol. 346 (1): 83-89.

Chang, F.K., Sato, N., Simorowski, N.K., Yoshihara, T., Meth, J.L., and Hamaguchi, M. (2006): DBC2 is Essential for Transporting Vesicular Stomatitis Virus Glycoprotein. J. Mol. Biol. 364 (3): 302-308.

Yoshihara, Y., Collado, D. and Hamaguchi, M. (2007): "Cyclin D1 Down-regulation is Essential for DBC2's Tumor Suppressor Function." Biochem. Biophys. Res. Commun. 358 (4): 1076-1079.

Collado, D., Yoshihara, Y. and Hamaguchi, M. (2007): "DBC2 Resistance is Achieved by Enhancing 26S Proteasome-mediated Protein Degradation." Biochem. Biophys. Res. 360: 600-603.