Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer
Annual summary rept. 1 Jun 2006-31 May 2007
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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Naure polyamines play an important role in cell proliferation and differentiation. Synthetic polyamine analogues can mimic natural polyamines in the down-regulation of polyamine biosynthesis, but analogues cannot promote cell growth. Our previous results show that polyamine analogues also down-regulate estrogen receptor ER , the principle target in human breast cancer therapy. This proposal was designed to investigate the molecular mechanisms and the therapeutic efficacy of oligomines in the treatment of human breast cancer. In the fourth year of this award, we investigated the possible roles of the polyamines biosynthetic pathway in polyamine analogues mediated repress on ER . In our latest studies, we demonstrated that ER expression was repressed after ornithine decarboxylase ODC, the polyamines biosynthetic key enzyme, was downregulated by siRNA in several human breast cancer cell lines. Apoptosis and cell cycle arrest were also induced. These results indicated that the polyamine synthetic pathway is a key mediator of polyamine analogue induced ER alpha suppression.
- Medicine and Medical Research