TY - JOUR
T1 - Phenotypic features of breast cancer cells overexpressing ornithine‐decarboxylase
AU - Manni, Andrea
AU - Wechter, Rita
AU - Wei, Lisa
AU - Heitjan, Daniel
AU - Demers, Laurence
PY - 1995/4
Y1 - 1995/4
N2 - Polyamines (PA) have been shown to be critical mediators of estradiol‐induced breast cancer cell proliferation. This finding suggests that constitutive activation of the PA pathway may promote tumor progression, possibly leading to hormone independence. To test this hypothesis, we transfected hormone‐responsive MCF‐7 breast cancer cells with a complementary DNA coding for ornithine‐decarboxylase (ODC), the first rate‐limiting enzyme in PA biosynthesis. Marked ODC over‐expression observed in stably transfected clones was associated with a selective increase in cellular putrescine content, while spermidine and spermine levels were not altered. ODC‐overexpressing MCF‐7 cells were resistant to the antiproliferative effects of low but not high concentrations of the enzyme inhibitor, α‐difluoromethylornithine. In agreement with our hypothesis, sensitivity to the growth‐promoting action of estradiol was reduced by approximately one third (P < 0.001) in ODC‐overexpressing MCF‐7 cells compared with vector‐only transfected clones. Basal growth under anchorage‐dependent conditions was only marginally increased by ODC overexpression (P = 0.048), while clonogenicity in soft agar was actually reduced. These data suggest that activation of PA biosynthesis may contribute in part to the acquisition of estrogen independence by breast cancer cells. Since only putrescine content was increased as a result of ODC overexpression, these data may underestimate the overall influence of the PA pathway on breast cancer phenotype. © 1995 Wiley‐Liss, Inc.
AB - Polyamines (PA) have been shown to be critical mediators of estradiol‐induced breast cancer cell proliferation. This finding suggests that constitutive activation of the PA pathway may promote tumor progression, possibly leading to hormone independence. To test this hypothesis, we transfected hormone‐responsive MCF‐7 breast cancer cells with a complementary DNA coding for ornithine‐decarboxylase (ODC), the first rate‐limiting enzyme in PA biosynthesis. Marked ODC over‐expression observed in stably transfected clones was associated with a selective increase in cellular putrescine content, while spermidine and spermine levels were not altered. ODC‐overexpressing MCF‐7 cells were resistant to the antiproliferative effects of low but not high concentrations of the enzyme inhibitor, α‐difluoromethylornithine. In agreement with our hypothesis, sensitivity to the growth‐promoting action of estradiol was reduced by approximately one third (P < 0.001) in ODC‐overexpressing MCF‐7 cells compared with vector‐only transfected clones. Basal growth under anchorage‐dependent conditions was only marginally increased by ODC overexpression (P = 0.048), while clonogenicity in soft agar was actually reduced. These data suggest that activation of PA biosynthesis may contribute in part to the acquisition of estrogen independence by breast cancer cells. Since only putrescine content was increased as a result of ODC overexpression, these data may underestimate the overall influence of the PA pathway on breast cancer phenotype. © 1995 Wiley‐Liss, Inc.
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U2 - 10.1002/jcp.1041630115
DO - 10.1002/jcp.1041630115
M3 - Article
C2 - 7896889
AN - SCOPUS:0028911727
SN - 0021-9541
VL - 163
SP - 129
EP - 136
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -