Polyamine Analogues as Novel Anti-HER Family Agents in Human Breast Cancer
Annual summary rept. 29 Sep 2007-28 Aug 2008
JOHNS HOPKINS UNIV BALTIMORE MD SCHOOL OF MEDICINE
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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 PG-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 receptorER-alpha protein in multiple human breast cancer cell lines. This downregulation occurred with the 24 hour treatment of T47D cells. These studies were extended to evaluate the effects of long term, low dose exposure of PG-11144 in T47D cells downregulation was observed in HER family protein and RNA levels. 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.
- Medicine and Medical Research