Multihormonal regulation of the progesterone receptor in mcf-7 human breast cancer cells: Interrelationships among insulin/insulin-like growth factor-i, serum, and estrogen

Benita S Katzenellenbogen, Mary Jane Norman

Research output: Contribution to journalArticle

Abstract

Estrogen (E) is well known to be an important stimulator of progesterone receptor (PR) synthesis in target cells. We have observed that E stimulation of PR in MCF-7 human breast cancer cells (as monitored by progestin binding or Western blotting with anti-PR antibodies) increases as a function of serum concentration in the cell culture medium; PR stimulation by E is greatest in high serum medium (5% or 10% charcoal dextran-treated calf serum) and is not observed when cells are in medium containing serum concentrations below 1%, although estrogen receptor levels are well maintained. This suggests that some serum factor(s) may be essential for E to be able to stimulate PR. To better understand such factors, we have grown cells in serum-free medium and in serum-free medium supplemented with insulin (6.25 ng/ml), transferrin (6.25 µg/ml), selenium (6.25 ng/ml), albumin (1.25 ng/ml), and linoleic acid (5.35 µg/ml; ITS+). Unexpectedly, we found that addition of ITS+ (without E) increases PR levels in these cells, especially in the absence of serum and under low serum conditions where E stimulation of PR is poor. Analyses of the individual components in ITS+ reveal that insulin is the major active component. Dose-response studies indicate that high superphysiological (>1 µg/ml) concentrations of insulin are required. In contrast, low physiological levels of insulin-like growth factor-I (IGF-I; 10 or 40 ng/ml) are active, suggesting mediation by the IGF type I receptor system. At all serum concentrations (0-10%), the effects of ITS+ and E in increasing PR are synergistic. The fact that anti-E are able to suppress the insulin/IGFI stimulation as well as the E stimulation of PR suggests that the anti-E can actively interfere with the action of the growth factor as well as the action of E. These results indicate that regulation of PR is multifactor and raise the possibility that PR may be regulated in vivo by both E and growth factors such as IGF-I that are known to be increased in these breast cancer cells by E.

Original languageEnglish (US)
Pages (from-to)891-898
Number of pages8
JournalEndocrinology
Volume126
Issue number2
DOIs
StatePublished - Feb 1990

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Somatomedins
Progesterone Receptors
Estrogens
Insulin
Breast Neoplasms
Serum
Insulin-Like Growth Factor I
Serum-Free Culture Media
Intercellular Signaling Peptides and Proteins
IGF Type 1 Receptor
Charcoal
Linoleic Acid
Progestins
Transferrin
Selenium
Dextrans
Estrogen Receptors
Culture Media
Albumins
Cell Culture Techniques

ASJC Scopus subject areas

  • Endocrinology

Cite this

@article{62d53f582e23408ca68c77c541687f49,
title = "Multihormonal regulation of the progesterone receptor in mcf-7 human breast cancer cells: Interrelationships among insulin/insulin-like growth factor-i, serum, and estrogen",
abstract = "Estrogen (E) is well known to be an important stimulator of progesterone receptor (PR) synthesis in target cells. We have observed that E stimulation of PR in MCF-7 human breast cancer cells (as monitored by progestin binding or Western blotting with anti-PR antibodies) increases as a function of serum concentration in the cell culture medium; PR stimulation by E is greatest in high serum medium (5{\%} or 10{\%} charcoal dextran-treated calf serum) and is not observed when cells are in medium containing serum concentrations below 1{\%}, although estrogen receptor levels are well maintained. This suggests that some serum factor(s) may be essential for E to be able to stimulate PR. To better understand such factors, we have grown cells in serum-free medium and in serum-free medium supplemented with insulin (6.25 ng/ml), transferrin (6.25 µg/ml), selenium (6.25 ng/ml), albumin (1.25 ng/ml), and linoleic acid (5.35 µg/ml; ITS+). Unexpectedly, we found that addition of ITS+ (without E) increases PR levels in these cells, especially in the absence of serum and under low serum conditions where E stimulation of PR is poor. Analyses of the individual components in ITS+ reveal that insulin is the major active component. Dose-response studies indicate that high superphysiological (>1 µg/ml) concentrations of insulin are required. In contrast, low physiological levels of insulin-like growth factor-I (IGF-I; 10 or 40 ng/ml) are active, suggesting mediation by the IGF type I receptor system. At all serum concentrations (0-10{\%}), the effects of ITS+ and E in increasing PR are synergistic. The fact that anti-E are able to suppress the insulin/IGFI stimulation as well as the E stimulation of PR suggests that the anti-E can actively interfere with the action of the growth factor as well as the action of E. These results indicate that regulation of PR is multifactor and raise the possibility that PR may be regulated in vivo by both E and growth factors such as IGF-I that are known to be increased in these breast cancer cells by E.",
author = "Katzenellenbogen, {Benita S} and Norman, {Mary Jane}",
year = "1990",
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AU - Katzenellenbogen, Benita S

AU - Norman, Mary Jane

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N2 - Estrogen (E) is well known to be an important stimulator of progesterone receptor (PR) synthesis in target cells. We have observed that E stimulation of PR in MCF-7 human breast cancer cells (as monitored by progestin binding or Western blotting with anti-PR antibodies) increases as a function of serum concentration in the cell culture medium; PR stimulation by E is greatest in high serum medium (5% or 10% charcoal dextran-treated calf serum) and is not observed when cells are in medium containing serum concentrations below 1%, although estrogen receptor levels are well maintained. This suggests that some serum factor(s) may be essential for E to be able to stimulate PR. To better understand such factors, we have grown cells in serum-free medium and in serum-free medium supplemented with insulin (6.25 ng/ml), transferrin (6.25 µg/ml), selenium (6.25 ng/ml), albumin (1.25 ng/ml), and linoleic acid (5.35 µg/ml; ITS+). Unexpectedly, we found that addition of ITS+ (without E) increases PR levels in these cells, especially in the absence of serum and under low serum conditions where E stimulation of PR is poor. Analyses of the individual components in ITS+ reveal that insulin is the major active component. Dose-response studies indicate that high superphysiological (>1 µg/ml) concentrations of insulin are required. In contrast, low physiological levels of insulin-like growth factor-I (IGF-I; 10 or 40 ng/ml) are active, suggesting mediation by the IGF type I receptor system. At all serum concentrations (0-10%), the effects of ITS+ and E in increasing PR are synergistic. The fact that anti-E are able to suppress the insulin/IGFI stimulation as well as the E stimulation of PR suggests that the anti-E can actively interfere with the action of the growth factor as well as the action of E. These results indicate that regulation of PR is multifactor and raise the possibility that PR may be regulated in vivo by both E and growth factors such as IGF-I that are known to be increased in these breast cancer cells by E.

AB - Estrogen (E) is well known to be an important stimulator of progesterone receptor (PR) synthesis in target cells. We have observed that E stimulation of PR in MCF-7 human breast cancer cells (as monitored by progestin binding or Western blotting with anti-PR antibodies) increases as a function of serum concentration in the cell culture medium; PR stimulation by E is greatest in high serum medium (5% or 10% charcoal dextran-treated calf serum) and is not observed when cells are in medium containing serum concentrations below 1%, although estrogen receptor levels are well maintained. This suggests that some serum factor(s) may be essential for E to be able to stimulate PR. To better understand such factors, we have grown cells in serum-free medium and in serum-free medium supplemented with insulin (6.25 ng/ml), transferrin (6.25 µg/ml), selenium (6.25 ng/ml), albumin (1.25 ng/ml), and linoleic acid (5.35 µg/ml; ITS+). Unexpectedly, we found that addition of ITS+ (without E) increases PR levels in these cells, especially in the absence of serum and under low serum conditions where E stimulation of PR is poor. Analyses of the individual components in ITS+ reveal that insulin is the major active component. Dose-response studies indicate that high superphysiological (>1 µg/ml) concentrations of insulin are required. In contrast, low physiological levels of insulin-like growth factor-I (IGF-I; 10 or 40 ng/ml) are active, suggesting mediation by the IGF type I receptor system. At all serum concentrations (0-10%), the effects of ITS+ and E in increasing PR are synergistic. The fact that anti-E are able to suppress the insulin/IGFI stimulation as well as the E stimulation of PR suggests that the anti-E can actively interfere with the action of the growth factor as well as the action of E. These results indicate that regulation of PR is multifactor and raise the possibility that PR may be regulated in vivo by both E and growth factors such as IGF-I that are known to be increased in these breast cancer cells by E.

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