Head and neck squamous cell carcinomas (SCCHN) have one of the highest frequencies of gene amplification in human cancers. Amplification of chromosomal band 11q13 is observed in approximately 45 percent of SCCHN (compared to approximately 15-25 percent of other carcinomas) and is associated with a poor prognosis. The literature has focused on cyclin D1 (CCND1) and cortactin (EMS1) driving amplification and tumor progression. However, our preliminary data indicate that seven, not two genes within the 11q13 amplicon are overexpressed. We hypothesize that the overexpression of multiple genes in 11q13 contributes to tumor progression. To test this, we propose to 1) determine which genes are overexpressed in SCCHN cell lines and primary tumors with and without amplification and 2) test the effects on gene expression and cellular phenotype of a) knockdown of the overexpression of specific genes and gene combinations using small interfering RNA (siRNA), and b) overexpression if specific genes and gene combinations in normal cells. This study can then be extended to other tumor types with 11q13 amplification, leading to a better understanding of the biology of disease, more accurate diagnostic tools, and possibly, targeted therapies. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA119725-01
Application #
7056962
Study Section
Special Emphasis Panel (ZRG1-F09 (20))
Program Officer
Lohrey, Nancy
Project Start
2006-08-01
Project End
2009-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
1
Fiscal Year
2006
Total Cost
$43,996
Indirect Cost
Name
University of Pittsburgh
Department
Genetics
Type
Schools of Public Health
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Henson, Brian J; Bhattacharjee, Samsiddhi; O'Dee, Dawn M et al. (2009) Decreased expression of miR-125b and miR-100 in oral cancer cells contributes to malignancy. Genes Chromosomes Cancer 48:569-82