POLYAMINE PROFILES AND GROWTH-PROPERTIES OF ORNITHINE DECARBOXYLASE OVEREXPRESSING MCF-7 BREAST-CANCER CELLS IN CULTURE

To determine the direct influence of the polyamine (PA) pathway on bre ast cancer phenotype, we employed a transfection approach to induce ov erexpression of the PA biosynthetic enzyme ornithine decarboxylase (OD C) in the hormone-responsive MCF-7 breast cancer cell line. Using a mo dified calcium phosphate method and an ODC cDNA coding for a truncated and more stable enzyme, we were able to achieve a moderate to marked degree of ODC overexpression (up to 150-fold) in a transient transfect ion system. ODC-overexpressing MCF-7 cells exhibited a selective incre ase in cellular putrescine content, while the levels of spermidine and spermine remained unaffected. Under defined culture conditions, overe xpression of ODC resulted in a consistent but modest increase in [H-3] thymidine incorporation into DNA which was similar in the presence and absence of 17-beta-estradiol, TGF-alpha, and IGF-I. In the presence o f serum, the effect of ODC overexpression on basal [H-3]-thymidine inc orporation into DNA was inconsistent, possibly as a result of subtle d ifferences in culture conditions. Overall, our results support the hyp othesis that activation of the PA biosynthetic pathway may confer a gr owth advantage to breast cancer cells.