INVOLVEMENT OF THE POLYAMINE PATHWAY IN BREAST-CANCER PROGRESSION

These experiments were designed to test the role of the polyamine path way in breast cancer progression utilizing an experimental system base d on the development of ovary-independent rat mammary tumors and their sequential transplantation into syngeneic hosts. Three key enzymes in volved in the PA biosynthetic/catabolic pathway (ornithine-decarboxyla se (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine/s permine N'-acetyltransferase (SSAT)) were measured in tumors at differ ent stages of progression. The most significant finding was the associ ation between increased ODC activity and the acquisition of a hormone- independent, poorly differentiated phenotype. SSAT levels tended to be higher in hormone-independent tumors and, in this tumor category, the y tended to be positively correlated with differentiation. However, si gnificant interaction between hormone dependence and differentiation s tatus on SSAT expression prevented reliable assessment of the possibly complex role of this enzyme in tumor progression. Neither hormone dep endence nor differentiation status were correlated with SAMDC levels. We conclude that, among the three enzymes tested, ODC overexpression i s the most significant alteration in the PA metabolic pathway associat ed with breast cancer progression in this experimental system.