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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 overexpression 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, alpha-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.
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
March 2008,
Acta biochimica et biophysica Sinica,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
November 2003,
Journal of biochemistry,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
August 1995,
Cancer letters,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
November 2021,
Breast cancer research and treatment,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
June 1998,
The European journal of neuroscience,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
January 2009,
Familial cancer,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
November 1989,
Cancer research,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
September 2003,
BMC cancer,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
November 1991,
Breast cancer research and treatment,
A Manni, and
R Wechter, and
L Wei, and
D Heitjan, and
L Demers
January 1984,
Cell biochemistry and function,
