Elevated levels of all three naturally occurring polyamines, spermine, spermidine and putrescine, have been found in breast cancer tissues. Polyamine analogues have been shown to inhibit cell growth and in some cases induce apoptosis. My studies have demonstrated the ability of CGC-11144 and other oligoamines to inhibit cell growth in human breast cancer cell lines. These oligamines can also suppress epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2) and estrogen receptor(ER)-alpha protein in multiple human breast cancer cell lines. This suppression is both time and dose dependent. A relationship between oligoamine structure, growth inhibition, and suppression of EGFR and HER2 protein expression seems to exist, with higher nitrogen compounds have the greatest effect. This project will demonstrate that oligoamines are novel anti-HER family agents and oligoamine-induced down regulation of HER family members contributes to their cytotoxicity in human breast cancer cell lines. The completion of this project will also provide valuable information about the potential clinical application of oligoamines
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