Role of Nucleosome Remodeling Factor (NURF) in Tumorigenesis Using a Breast Cancer Mouse Model

Understanding the impact of epigenetic mechanisms on tumorigenesis is essential, as epigenetic alterations are associated with tumor initiation and progression. Because epigenetic changes are reversible, they are potential targets for cancer therapy. Nucleosome Remodeling Factor (NURF) is a chromatin-remodeling complex that regulates gene expression by changing nucleosome positioning along the DNA sequence. Previous studies have shown a role for NURF in embryonic development as well as regulating genes involved in tumor progression. In this work we investigated the impact of eliminating NURF function in tumorigenesis in vivo. BALB/c mice challenged with syngeneic 67NR breast cancer cell lines, injected into the mammary fat pad, lacking NURF, due to knockdown of its essential subunits Bptf, showed reduction in tumor growth comparing to control tumors. The observed reduction in tumor growth was abrogated in immunodeficient mice lacking a functional immune system. Bptf KD and control 67NR cells grew at similar rates in vitro. Similar findings were observed in our lab using 66cl4 breast cancer cell lines. Using immunofluorescence staining, no significant difference in CD8+, CD4+, NK and MDSC cells infiltrations into the tumor microenvironment was observed in 66cl4 tumors. Preliminary results from 67NR tumors suggested more CD4+ and CD8+ cells. Gene expression profile of tumor tissues from BALB/c mice injected with 67NR and 66cl4 cell lines showed enrichment of genes associated with immune response. Our findings suggested a role of the immune system in targeting tumor cells lacking Bptf in vivo.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Human Genetics

Year dc:date.available

2012

Author dc:creator

• Alhazmi, Aiman

Contributors dc:contributor

• Joseph Landry

• NURF
• Immunosurveillance
• Epigenetics
• Immune System
• Cancer
• Medical Genetics
• Medical Sciences
• Medicine and Health Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/379

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1378