Relationship between the expression of estrogen-regulated genes and estrogen-stimulated proliferation of MCF-7 mammary tumor cells

S. C. Aitken, Marc E Lippman, A. Kasid, D. R. Schoenberg

Research output: Contribution to journalArticle

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Abstract

The growth of MCF-7 cells was arrested by 24 h of isoleucine deprivation. Following replenishment of the medium, the incorporation of uridine and thymidine into trichloroacetic acid-precipitable material began to increase slowly and gradually rose to the level of cycling cells. The addition of 5 x 10-9 M estradiol to growth-arrested cells dramatically shortened the time of onset of macromolecular synthesis and increased the overall amount of precursor incorporation 2- to 4-fold over the level obtained by arrested control cells. The increase in uridine incorporation preceded the increase in thymidine incorporation by 6 h. Inhibition of protein synthesis with cycloheximide blocked the recovery of macromolecular synthesis in both control and estrogen-treated cells. Actinomycin D was ineffective in blocking the estrogen-stimulated recovery of macromolecular synthesis at concentrations known to inhibit pre-rRNA synthesis (10-8 M). At higher concentrations, uridine and thymidine incorporation were inhibited in a dose-dependent manner. Inhibition of RNA polymerase II activity with α-amanitin similarly blocked the recovery of the cells from isoleucine starvation and the potentiation of this by estradiol. Dihydrofolate reductase and thymidine kinase activities are both stimulated by estradiol in MCF-7 cells. In cycling cells, estrogen stimulates a 2-fold increase in their messenger RNAs (mRNAs) within 24 h. The level of dihydrofolate reductase mRNA is unaffected by isoleucine starvation, and estrogen caused no change in dihydrofolate reductase mRNA levels over a 24-h period following reversal of growth arrest. Similar results were observed for the 600-nucleotide pS2 mRNA that has been identified as an estrogen-induced RNA in MCF-7 cells. In contrast, thymidine kinase mRNA was found to be increased by estrogen at 24 h, but not at 12 h, following reversal of growth arrest. This increase correlates with increases in thymidine, but not uridine incorporation. These data indicate that the estrogen-stimulated increase in thymidine incorporation following release from growth arrest is dependent on new RNA synthesis. However, the hormone did not increase the levels of three estrogen-regulated mRNAs coordinately with the increases observed in uridine incorporation.

Original languageEnglish
Pages (from-to)2608-2615
Number of pages8
JournalCancer Research
Volume45
Issue number6
StatePublished - Jan 1 1985
Externally publishedYes

Fingerprint

Estrogens
Uridine
Breast Neoplasms
Thymidine
Messenger RNA
Tetrahydrofolate Dehydrogenase
Genes
Isoleucine
MCF-7 Cells
Growth
Estradiol
Thymidine Kinase
Starvation
RNA
Amanitins
Trichloroacetic Acid
RNA Polymerase II
RNA Precursors
Dactinomycin
Cycloheximide

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Relationship between the expression of estrogen-regulated genes and estrogen-stimulated proliferation of MCF-7 mammary tumor cells. / Aitken, S. C.; Lippman, Marc E; Kasid, A.; Schoenberg, D. R.

In: Cancer Research, Vol. 45, No. 6, 01.01.1985, p. 2608-2615.

Research output: Contribution to journalArticle

Aitken, S. C. ; Lippman, Marc E ; Kasid, A. ; Schoenberg, D. R. / Relationship between the expression of estrogen-regulated genes and estrogen-stimulated proliferation of MCF-7 mammary tumor cells. In: Cancer Research. 1985 ; Vol. 45, No. 6. pp. 2608-2615.
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