Abstract

A novel gene, DBC2, was recently isolated and preliminary studies of DBC2 indicate that it is a potential candidate for a tumor suppressor. The long-term objectives include genetic analysis of DBC2 to validate it as a tumor suppressor; functional analysis of DBC2 to clarify physiological and pathological roles of DBC2; and studies of tumor physiology of DBC2 to provide new insights to breast and lung cancer development, The goal of this research project is to test the hypothesis that DBC2 is a tumor suppressor gene, Specific aims are:
Specific Aim 1. We will utilize inducible gene expression systems to test the DBC2 function in vitro. Mutations will be introduced into predicted functional domains. Wild type and mutated DBC2 will be induced into various types of cells. Alterations of phenotypes and expression patterns will be analyzed.
Specific Aim 2. Transcriptional regulation of DBC2 in cancer will be studied, Expression of DBC2 and the methylation status of the DBC2 promoter region will be investigated in cell lines and primary tumors.
Specific Aim3. We will lay the foundations for studies on cellular functions of DBC2. Antibodies against DBC2 will be generated, Physiological expression of DBC2 in various tissues will be analyzed.
Specific Aim 4. We will use embryonic stem (ES) cell technology to generate a Dbc2-deficient mouse model and analyze these mice for tumor susceptibility. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA100006-02
Application #
6879046
Study Section
Pathology B Study Section (PTHB)
Program Officer
Yassin, Rihab R,
Project Start
2004-04-01
Project End
2005-08-31
Budget Start
2005-04-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$219,975
Indirect Cost

  Institution

Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724

  Publications

Collado, Denise; Yoshihara, Takashi; Hamaguchi, Masaaki (2007) DBC2 resistance is achieved by enhancing 26S proteasome-mediated protein degradation. Biochem Biophys Res Commun 360:600-3
Yoshihara, Takashi; Collado, Denise; Hamaguchi, Masaaki (2007) Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function. Biochem Biophys Res Commun 358:1076-9
Chang, Faith K; Sato, Noriko; Kobayashi-Simorowski, Noriko et al. (2006) DBC2 is essential for transporting vesicular stomatitis virus glycoprotein. J Mol Biol 364:302-8
Siripurapu, Veeraiah; Meth, Jennifer; Kobayashi, Noriko et al. (2005) DBC2 significantly influences cell-cycle, apoptosis, cytoskeleton and membrane-trafficking pathways. J Mol Biol 346:83-9