Phenotypic features of breast cancer cells overexpressing ornithine‐decarboxylase

Andrea Manni, Rita Wechter, Lisa Wei, Daniel Heitjan, Laurence Demers

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalJournal of Cellular Physiology
Volume163
Issue number1
DOIs
StatePublished - Jan 1 1995

Fingerprint

Polyamines
Cells
Breast Neoplasms
Putrescine
Biosynthesis
MCF-7 Cells
Clone Cells
Chemical activation
Eflornithine
Spermidine
Spermine
Cell proliferation
Enzyme Inhibitors
Agar
Tumors
Estradiol
Estrogens
Complementary DNA
Cell Proliferation
Hormones

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Phenotypic features of breast cancer cells overexpressing ornithine‐decarboxylase. / Manni, Andrea; Wechter, Rita; Wei, Lisa; Heitjan, Daniel; Demers, Laurence.

In: Journal of Cellular Physiology, Vol. 163, No. 1, 01.01.1995, p. 129-136.

Research output: Contribution to journalArticle

Manni, Andrea ; Wechter, Rita ; Wei, Lisa ; Heitjan, Daniel ; Demers, Laurence. / Phenotypic features of breast cancer cells overexpressing ornithine‐decarboxylase. In: Journal of Cellular Physiology. 1995 ; Vol. 163, No. 1. pp. 129-136.
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