In female mammals, one of the two X-chromosomes is transcriptionally silenced through an epigenetic process known as X-chromosome inactivation (XCI). This dosage compensation mechanism ensures equal X-linked gene expression between XX females and XY males, and is necessary for normal development. A large body of experimental observations over the past several decades has implicated a role for XCI mis-regulation in the development and pathogenesis of various cancers, particularly female breast and reproductive cancers. First, loss of the Barr body -- a cytological signature of an inactivated X-chromosome -- has often been described for many female tumors. Second, X-chromosome anomalies, most often characterized by the gain of one or more transcriptionally active X-chromosomes and/or reactivation of the inactive X is a common phenomenon observed in many tumor cells. Third, the tumor suppressor, BRCA1, implicated in familial breast and ovarian cancers, has a role in X-chromosome inactivation. The objective of the proposed study is to investigate the role of X-chromosome reactivation in breast tumorigenesis. The long-term goal is to elucidate the role of X-linked genes in tumor development and pathogenesis.
The specific aims are: 1) to determine the role of ectopic X-linked expression in breast tumorigenesis using a mouse model system; 2) to identify and characterize X-linked genes overexpressed in breast tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01CA115593-02
Application #
7128539
Study Section
Subcommittee G - Education (NCI)
Program Officer
Ojeifo, John O
Project Start
2005-09-30
Project End
2010-08-31
Budget Start
2006-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2006
Total Cost
$97,043
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199