Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells

Xiangyan Ruan, Helen Schneck, Silke Schultz, Tanja Fehm, Michael Cahill, Harald Seeger, R Chen, Q Yu, Alfred O Mueck, Hans Neubauer

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Abstract

Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer. Methods: MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously. Results: E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist. Conclusion: Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.
Original languageEnglish
Pages (from-to)863-866
Number of pages4
JournalGynecological Endocrinology
Volume28
Issue number11
DOIs
Publication statusPublished - Nov 2012

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nomegestrol acetate
Norethindrone
Estradiol
Progesterone Receptors
Breast Neoplasms
Medroxyprogesterone Acetate
Membranes
Progestins
Cell Proliferation
MCF-7 Cells
Contraceptive Agents
Contraception
Progesterone
Plasmids

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Ruan, Xiangyan ; Schneck, Helen ; Schultz, Silke ; Fehm, Tanja ; Cahill, Michael ; Seeger, Harald ; Chen, R ; Yu, Q ; Mueck, Alfred O ; Neubauer, Hans. / Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells. In: Gynecological Endocrinology. 2012 ; Vol. 28, No. 11. pp. 863-866.
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title = "Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells",
abstract = "Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer. Methods: MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously. Results: E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200{\%}. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist. Conclusion: Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.",
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Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells. / Ruan, Xiangyan; Schneck, Helen; Schultz, Silke; Fehm, Tanja; Cahill, Michael; Seeger, Harald; Chen, R; Yu, Q; Mueck, Alfred O; Neubauer, Hans.

In: Gynecological Endocrinology, Vol. 28, No. 11, 11.2012, p. 863-866.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nomegestrol acetate sequentially or continuously combined to estradiol did not negatively affect membrane-receptor associated progestogenic effects in human breast cancer cells

AU - Ruan, Xiangyan

AU - Schneck, Helen

AU - Schultz, Silke

AU - Fehm, Tanja

AU - Cahill, Michael

AU - Seeger, Harald

AU - Chen, R

AU - Yu, Q

AU - Mueck, Alfred O

AU - Neubauer, Hans

N1 - Imported on 12 Apr 2017 - DigiTool details were: month (773h) = November, 2012; Journal title (773t) = Gynecological Endocrinology. ISSNs: 0951-3590;

PY - 2012/11

Y1 - 2012/11

N2 - Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer. Methods: MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously. Results: E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist. Conclusion: Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.

AB - Recently the first monophasic contraceptive pill containing estradiol has been developed which is thought to be a milestone in contraception. Nomegestrol acetate (NOM) is the progestogenic component. Progesterone receptor membrane component 1 (PGRMC1) is highly expressed in the tissue of breast cancer patients, and can predict a progestogen dependent risk of breast cancer. Methods: MCF-7 cells were transfected with PGRMC1 expression plasmid, and were stimulated with estradiol (E2, 10(-12) and 10(-10) M). NOM, progesterone (P), medroxyprogesterone acetate (MPA) and norethisterone (NET) (each 10(-7) M) were added sequentially or continuously. Results: E2 at 10(-10) M elicited a significant increase of cell proliferation from 150 to 200%. No effect was seen at 10(-12) M. Addition of the progestogens to E2 at 10(-10) M had no significant effect. However, at an E2 10(-12) M, NET significantly stimulated cell proliferation more pronounced in the continuous combined model. No effect was seen for NOM, P and MPA. The E2/NET combined effect could be abrogated by the addition of an estrogen receptor (ER) antagonist. Conclusion: Since NOM did not increase proliferation it may be concluded that it will be neutral in terms of breast cancer risk when combined with E2 at least in women overexpressing PGRMC1.

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DO - 10.3109/09513590.2012.671396

M3 - Article

VL - 28

SP - 863

EP - 866

JO - Gynecological Endocrinology

JF - Gynecological Endocrinology

SN - 0951-3590

IS - 11

ER -