Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 11, Pages 4408-4413Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0809130106
Keywords
REST; substance P; tachykinin
Categories
Funding
- Department of Defense, University Cancer Center
- New Jersey Cancer Commission
Ask authors/readers for more resources
Breast cancer remains the most prevalent cancer among women in the United States. Substance P, a peptide derived from the TAC1 gene, mediates oncogenic properties in breast and other cancers. TAC1 expression facilitates the entry of breast cancer cells into bone marrow. The transcriptional repressor element 1-silencing transcription factor (REST) has been implicated in both oncogenic and tumor-suppressor functions. REST binds to the 5' untranslated region of the TAC1 promoter and suppresses its expression. This study investigated a role for REST in TAC1 induction in breast cancer. Western blots and real-time PCR indicated that REST expression in breast cancer cells was inversely proportional to the cells' aggressiveness, for both cell lines and primary breast cancer cells. REST knockdown in low-metastatic T47D cells and nontumorigenic MCF12A cells resulted in increases in TAC1 induction, proliferation, and migration. These parameters were negatively affected by ectopic expression of REST in highly aggressive MDA-MB-231 cells. Together, these findings show a central role for REST in the oncogenic function of TAC1 and suggest a tumor-suppressor role for REST in breast cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available