Involvement of the polyamine pathway in breast cancer progression.

These experiments were designed to test the role of the polyamine pathway in breast cancer progression utilizing an experimental system based on the development of ovary-independent rat mammary tumors and their sequential transplantation into syngeneic hosts. Three key enzymes involved in the PA biosynthetic/catabolic pathway (ornithine-decarboxylase (ODC), S-adenosylmethionine decarboxylase (SAMDC), and spermidine/spermine N'-acetyltransferase (SSAT)) were measured in tumors at different stages of progression. The most significant finding was the association 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, they tended to be positively correlated with differentiation. However, significant interaction between hormone dependence and differentiation status on SSAT expression prevented reliable assessment of the possibly complex role of this enzyme in tumor progression. Neither hormone dependence nor differentiation status were correlated with SAMDC levels. We conclude that, among the three enzymes tested, ODC overexpression is the most significant alteration in the PA metabolic pathway associated with breast cancer progression in this experimental system.