Hormonal regulation of the novo pyrimidine synthesis and ultilization in human breast cancer cells in tissue culture

S. C. Aitken, Marc E Lippman

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The hormonal regulation of pyrimidine synthesis and utilization is examined in the estrogen-responsive MCF-7 human breast cancer cell line. [14C]Acetate is used as a novel marker in assaying the incorporation of pyrimidine nucleotides derived through de novo synthesis into DNA. Technical verification of the validity of this tracer in DNA synthesis is presented. The experimental conditions permitting extrapolation from radioactivity incorporated into DNA to pmol of DNA synthesized/unit of time are discussed. We observed that estrogen administration increases the incorporation of [14C]acetate into DNA, and this effect is most evident after 36 hr of exposure to hormone. Treatment with the antiestrogen tamoxifen produces substantial reductions in the rate of incorporation of [14C]acetate into DNA. Incorporation correlates well with net rates of DNA synthesis, as measured by 32P(i) incorporation into DNA. Concomitant administration of thymidine in concentrations in excess of 10-7 M partially relieves tamoxifen inhibition of net DNA synthesis and increases the apparent stimulation of net DNA synthesis following 18 to 32 hr of estrogen treatment. Activity of de novo enzymes such as carbamylphosphate synthetase, aspartate transcarbamylase, orotidine pyrophosphorylase, and orotidine decarboxylase also varies with hormone treatment. All characteristically increase following estrogen treatment and decrease after tamoxifen administration. These results suggest that changes in de novo pyrimidine synthesis after hormone treatment are directly linked to hormone-induced alterations in the activity of specific enzymes in the de novo pathway.

Original languageEnglish
Pages (from-to)4681-4690
Number of pages10
JournalCancer Research
Volume43
Issue number10
StatePublished - Jan 1 1983
Externally publishedYes

Fingerprint

Breast Neoplasms
DNA
Estrogens
Tamoxifen
Hormones
Acetates
Aspartate Carbamoyltransferase
pyrimidine
Pyrimidine Nucleotides
Carboxy-Lyases
Estrogen Receptor Modulators
Enzymes
Ligases
Thymidine
Radioactivity
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hormonal regulation of the novo pyrimidine synthesis and ultilization in human breast cancer cells in tissue culture. / Aitken, S. C.; Lippman, Marc E.

In: Cancer Research, Vol. 43, No. 10, 01.01.1983, p. 4681-4690.

Research output: Contribution to journalArticle

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