Molecular modulation of estrogen-induced apoptosis by synthetic progestins in hormone replacement therapy : an insight into the women's health initiative study
©2014 American Association for Cancer Research..
Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women and can be comprised of an estrogen alone or an estrogen combined with a progestin. The Women's Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in postmenopausal women, whereas combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the postmenopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone, increases glucocorticoid receptor (GR) transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting that it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, upregulating estrogen receptor target genes and generating apoptosis in MCF-7:5C cells. The data suggest that women taking HRT comprising an estrogen plus MPA may have an increased risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g., NETA) should be considered as alternatives to MPA.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2014 |
|---|---|
| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:74 |
|---|---|
| Enthalten in: |
Cancer research - 74(2014), 23 vom: 01. Dez., Seite 7060-8 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sweeney, Elizabeth E [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.03.2015 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1158/0008-5472.CAN-14-1784 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM242677606 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM242677606 | ||
| 003 | DE-627 | ||
| 005 | 20240322234442.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2014 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1158/0008-5472.CAN-14-1784 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1340.xml |
| 035 | |a (DE-627)NLM242677606 | ||
| 035 | |a (NLM)25304262 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sweeney, Elizabeth E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular modulation of estrogen-induced apoptosis by synthetic progestins in hormone replacement therapy |b an insight into the women's health initiative study |
| 264 | 1 | |c 2014 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 04.03.2015 | ||
| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2014 American Association for Cancer Research. | ||
| 520 | |a Hormone replacement therapy (HRT) is widely used to manage menopausal symptoms in women and can be comprised of an estrogen alone or an estrogen combined with a progestin. The Women's Health Initiative demonstrated in their randomized trials that estrogen alone HRT decreases the risk of breast cancer in postmenopausal women, whereas combined estrogen plus a progestin (medroxyprogesterone acetate, MPA) HRT increases this risk. Long-term estrogen-deprived MCF-7:5C cells were used to model the postmenopausal breast cancer cell environment. MPA is able to modify E2-induced apoptosis in MCF-7:5C cells. MPA, similar to dexamethasone, increases glucocorticoid receptor (GR) transcriptional activity, increases SGK1, a GR target gene, and can be blocked by RU486 (an antiglucocorticoid), suggesting that it functions through the GR. Norethindrone acetate (NETA), another progestin used in HRT, acts like an estrogen at high doses, upregulating estrogen receptor target genes and generating apoptosis in MCF-7:5C cells. The data suggest that women taking HRT comprising an estrogen plus MPA may have an increased risk of breast cancer due to MPA acting as a glucocorticoid and blunting E2-induced apoptosis in this environment. Therefore, perhaps other approved progestins (e.g., NETA) should be considered as alternatives to MPA | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a Estrogens |2 NLM | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a Progesterone Congeners |2 NLM | |
| 650 | 7 | |a Receptors, Estrogen |2 NLM | |
| 650 | 7 | |a Receptors, Glucocorticoid |2 NLM | |
| 650 | 7 | |a Mifepristone |2 NLM | |
| 650 | 7 | |a 320T6RNW1F |2 NLM | |
| 650 | 7 | |a Dexamethasone |2 NLM | |
| 650 | 7 | |a 7S5I7G3JQL |2 NLM | |
| 650 | 7 | |a Norethindrone Acetate |2 NLM | |
| 650 | 7 | |a 9S44LIC7OJ |2 NLM | |
| 650 | 7 | |a Medroxyprogesterone Acetate |2 NLM | |
| 650 | 7 | |a C2QI4IOI2G |2 NLM | |
| 650 | 7 | |a Norethindrone |2 NLM | |
| 650 | 7 | |a T18F433X4S |2 NLM | |
| 700 | 1 | |a Fan, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Jordan, V Craig |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cancer research |d 1945 |g 74(2014), 23 vom: 01. Dez., Seite 7060-8 |w (DE-627)NLM000001740 |x 1538-7445 |7 nnns |
| 773 | 1 | 8 | |g volume:74 |g year:2014 |g number:23 |g day:01 |g month:12 |g pages:7060-8 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1158/0008-5472.CAN-14-1784 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 74 |j 2014 |e 23 |b 01 |c 12 |h 7060-8 | ||