Galectin-7 is a beta-galactoside-binding animal lectin initially identified as a differentiation marker expressed in all types of stratified epithelia as well as a protein that is down modulated in SV-40 transformed keratinocytes. This protein has been found to be induced by p53 in a colorectal carcinoma cell line and designated as PIG1 (p53-induced gene-1). Our work has focused on the proapoptotic function of this protein, with an ultimate goal of developing a therapeutic approach to squamous cell carcinoma. We have studied the signaling pathway by which galectin-7 activates apoptotic function and found that JNK activation and mitochondrial cytochrome c release are responsible for the action mediated by galectin-7. Inducing activation of galectin-7 up-regulates differentiation- as well as apoptosis-related genes. Expressing this protein in colorectal carcinoma cells profoundly suppressed their tumor growth in vivo, indicating the potential for developing galectin-7 into strategy for cancer therapy. In this research proposal we will study: 1. Investigation of the effect of galectin-7 on cell growth and apoptosis in normal human keratinocytes: We will extend our previous mechanistic analysis on galectin-7's proapoptotic and growth-suppressive functions to the studies using normal human keratinocytes. For this, the gene knock-down approach using a short interfering RNA system will be pursued and various aspects of apoptosis will be analyzed. 2. Investigation of the antitumor functions of galectin-7 in squamous cell carcinoma: We will analyze galectin-7 expression in SCC specimens as well as cell lines with different degree of malignancy. Then, we will investigate galectin-7's potential impact on SCC by transfecting the galectin-7 gene into a SCC line and in vitro cell growth, apoptosis, and in vivo tumor growth will be evaluated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR050532-03
Application #
7061272
Study Section
Special Emphasis Panel (ZAR1-RJB-D (O1))
Program Officer
Baker, Carl
Project Start
2004-03-05
Project End
2007-02-28
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
3
Fiscal Year
2006
Total Cost
$72,505
Indirect Cost
Name
University of California Davis
Department
Dermatology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Ueda, Shugo; Kuwabara, Ichiro; Liu, Fu-Tong (2004) Suppression of tumor growth by galectin-7 gene transfer. Cancer Res 64:5672-6