The overall goal of this research is to investigate the hypothesis that dysregulated expression and function of Beta Protein 1 contributes to breast cancer pathogenesis. Dr. Berg cloned a novel homeobox gene called BP1 based upon its ability to repress human beta-globin gene expression. Expression of BP1 is highly restricted in normal tissues; however, data from our laboratory indicate that BP1 is overexpressed in hematopoietic cell lines and human immune cell cancers. In our more recent studies, increased BP1 expression was detected in breast cancer cell lines and human breast cancer samples. Together these data suggest that BP1 is a proto-oncogene. Most recently, we have initiated studies to examine the mechanism of BP1-mediated oncogenesis. Preliminary data support a regulatory role for BP1 in estrogen and retinoid signaling pathways. We plan to extend these preliminary results and further explore the interaction of BP1 with nuclear hormone signaling pathways in breast cancer. Specifically, we will: 1) Determine whether BP1 is expressed in benign breast tumors. 2) Study the effect of BP1 overexpression and BP1 antisense RNA on estrogen receptor ( gene expression in breast cells. 3) Functionally define the interactions of BP1 and ER transcriptional complex proteins in normal and neoplastic breast tissue. 4) Determine the effect of all-trans retinoic acid, 9-cis retinoic acid, estradiol, and the histone deacetylase inhibitor trichostatin A on breast cancer cells that overexpress BP1 compared to control cells. 5) Utilize microarray technology to determine the gene expression profile of breast cancer cells that overexpress BP1. I will design and conduct research at The George Washington University Medical Center, within the laboratory of Dr. Patricia Berg. I will also utilize the resources of the Genomics and Proteomics core facility directed by Dr. Tim McCaffrey. I propose to be trained by experienced investigators, namely Drs. Berg and McCaffrey, who will guide me during my transition from research trainee to independent molecular biologist. In addition, Drs. Schwartz, Fontana, and Ascensao will provide overarching scientific and career guidance and independent ongoing peer review. Finally, Dr. Schaffner will mentor my training in the responsible conduct of research.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08CA101875-01
Application #
6669894
Study Section
Subcommittee G - Education (NCI)
Program Officer
Myrick, Dorkina C
Project Start
2003-09-23
Project End
2008-08-31
Budget Start
2003-09-23
Budget End
2004-08-31
Support Year
1
Fiscal Year
2003
Total Cost
$133,650
Indirect Cost
Name
George Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052
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Mody, Manali; Dharker, Nachiket; Bloomston, Mark et al. (2007) Rosiglitazone sensitizes MDA-MB-231 breast cancer cells to anti-tumour effects of tumour necrosis factor-alpha, CH11 and CYC202. Endocr Relat Cancer 14:305-15
Stevenson, Holly S; Fu, Sidney W; Pinzone, Joseph J et al. (2007) BP1 transcriptionally activates bcl-2 and inhibits TNFalpha-induced cell death in MCF7 breast cancer cells. Breast Cancer Res 9:R60
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