RE-1-silencing transcription factor shows tumor-suppressor functions and negatively regulates the oncogenic TAC1 in breast cancer cells.
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.
Reddy
Bobby Y
BY
Department of Medicine-Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
Greco
Steven J
SJ
Patel
Prem S
PS
Trzaska
Katarzyna A
KA
Rameshwar
Pranela
P
D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D012720:Severity of Illness Index; D013373:Substance P / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D000099229:RE1-Silencing Transcription Factor
D012097:Repressor Proteins; D013373:Substance P; D025521:Tumor Suppressor Proteins; D000099229:RE1-Silencing Transcription Factor