TY - JOUR
T1 - Involvement of the polyamine pathway in breast cancer progression
AU - Manni, Andrea
AU - Grove, Rhea
AU - Kunselman, Susan
AU - Aldaz, Marcelo
N1 - Funding Information:
This work was supported by grants R-29-CA 48922 and PO1 CA4001 l-09 from the National Cancer Institute.
PY - 1995/5/25
Y1 - 1995/5/25
N2 - 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.
AB - 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.
KW - Breast cancer progression
KW - Ornithine decarboxylase
KW - Polyamines
KW - S-Adenosylmethionine decarboxylase
KW - Spermidine/spermine N′ acetyltrasferase
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U2 - 10.1016/0304-3835(95)03763-M
DO - 10.1016/0304-3835(95)03763-M
M3 - Article
C2 - 7757960
AN - SCOPUS:0029050065
SN - 0304-3835
VL - 92
SP - 49
EP - 57
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -