Pharmacological regulation of c-myc gene expression in human breast cancer cells

Previous studies demonstrated that quinidine causes G1/G0 cell cycle arrest and inhibition of proliferation in MCF-7 human breast cancer cell line (Woodfork, K. et al., 1995). The goal of studies reported here was to understand the molecular mechanisms of c-myc gene regulation by quinidine. C-myc is one of the most common oncogene aberrations in breast cancers (Deming, S. L. et al., 2000). C-myc functions include regulation of cell cycle, proliferation, differentiation, and apoptosis. The results of these studies demonstrated that quinidine causes rapid (within 1 hour) suppression of Myc protein and mRNA levels that precedes the quinidine-induced G1 cell cycle arrest point (D point) in MCF-7 cells. Additionally, the activity of c-myc promoter was suppressed by quinidine over the same range of concentrations that suppress levels of myc mRNA and protein, suggesting that changes in Myc protein and mRNA levels by quinidine may be attributed to its effect on myc promoter. A 168 by region of c-myc promoter (-100 to +68 in respect to P1) was identified as a quinidine responsive region (QRR). Suppression of Myc by quinidine was consistent with inhibition of growth and induction of more differentiated phenotype in four different breast tumor cell lines. In contrast, quinidine had minimal effect on Myc levels or proliferation in normal mammary epithelial cell lines. Furthermore, MCF-7 cells treated with c-myc antisense oligonucleotides exhibited cytoplasmic lipid droplets, similarly to the quinidine-treated cells, suggesting that suppression of Myc may play a causative role in the induction of more differentiated phenotype by quinidine in human breast cancer cells.

Name thesis:degree_name

PhD

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physiology, Pharmacology & Neuroscience

Year dc:date.available

2001

Author dc:creator

• Melkoumian, Zaroui Karlen

Contributors dc:contributor

• Jeannine S. Strobl.

• Pharmacology
• Oncology

Identifier

https://researchrepository.wvu.edu/etd/1440

OAI identifier oai:identifier

oai:researchrepository.wvu.edu:etd-2443