Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer
Abstract
The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism including a novel class of polyamine analogues, oligoamines. This proposal was designed to elucidate the molecular mechanisms and the therapeutic efficacy of oligoamines in treatment of human breast cancer. In the third year of this award, we demonstrated that oligoamines specifically suppress the expression of estrogen receptor (ER ) and its target genes. Further analysis demonstrated that oligoamines disrupted the DNA binding activity of Sp1 transcription factors to an ER minimal promoter element containing GC/CA rich boxes. Treatment of tumor cells with the JNK specific inhibitor SP600125, or expression of the c-Jun dominant negative inhibitor, TAM67, blocked the oligoamineactivated JNK/c-Jun pathway and enhanced oligoamine-inhibited ER expression, suggesting that AP-1 is a positive regulator of ER expression and that oligoamine activated JNK/AP-1 activity may antagonize the down-regulation of ER induced by oligoamines. These results suggest a novel antiestrogenic mechanism for specific polyamine analogues in human breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA460069
Entities
People
- Yi Huang
Organizations
- Johns Hopkins University