Estrone sulfate: A potential source of estradiol in human breast cancer tissues

Steven J. Santner, Donald Leszczynski, Carol Wright, Andrea Manni, Peter D. Feil, Richard J. Santen

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Local formation of estradiol in human breast tumors could provide a more important source of estrogen than is delivered from plasma. Prior studies have suggested that estrone is primarily synthesized from estrone sulfate. The enzyme 17β-hydroxysteroid dehydrogenase (HSD) would be required to convert estrone to estradiol. This study characterized HSD in 1000 × g supernatants from human breast tumors. Estradiol synthesis was linearly related to tissue concentration or time over the range studied. Cofactor requirements varied with estrone concentration. High and low affinity sites were found in 50% of tissues studied, while the remainder contained only low affinity sites. Screen assays showed measurable activity in all 42 samples tested. This activity ranged from 0.73->100 nmol estrone synthesized/g protein/hr, with a median activity of 5.9 nmol/g/hr. We evaluated the biological relevance of the sulfatase-HSD pathway by testing the ability of estrone sulfate to stimulate colony formation in soft agar cultures of nitrosomethylurea-induced rat mammary tumors. The maximally effective concentration ranged from 10-7 to 10-4 M. Significant stimulation of colony formation was observed in 7 of 8 experiments. The estrone sulfate stimulation pattern was similar to that previously observed with estradiol. Of the3H-estrone sulfate added to the dishes, 20-98% was recovered as estrone and 0.2-6% as estradiol. These studies suggest that the requisite enzymes are present in human breast tumors for conversion of estrone sulfate to estradiol, and that this pathway may be biologically significant.

Original languageEnglish (US)
Pages (from-to)35-44
Number of pages10
JournalBreast Cancer Research and Treatment
Volume7
Issue number1
DOIs
StatePublished - Feb 1 1986

Fingerprint

Estrone
Estradiol
Breast Neoplasms
Hydroxysteroid Dehydrogenases
Sulfatases
Methylnitrosourea
Enzymes
Agar
estrone sulfate
Estrogens
Proteins

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Santner, Steven J. ; Leszczynski, Donald ; Wright, Carol ; Manni, Andrea ; Feil, Peter D. ; Santen, Richard J. / Estrone sulfate : A potential source of estradiol in human breast cancer tissues. In: Breast Cancer Research and Treatment. 1986 ; Vol. 7, No. 1. pp. 35-44.
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Estrone sulfate : A potential source of estradiol in human breast cancer tissues. / Santner, Steven J.; Leszczynski, Donald; Wright, Carol; Manni, Andrea; Feil, Peter D.; Santen, Richard J.

In: Breast Cancer Research and Treatment, Vol. 7, No. 1, 01.02.1986, p. 35-44.

Research output: Contribution to journalArticle

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T2 - A potential source of estradiol in human breast cancer tissues

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AU - Leszczynski, Donald

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