{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:31:13Z","timestamp":1791894673772,"version":"4.3.4"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Progestins, synthetic compounds designed to mimic the activity of natural progesterone (P<jats:sub>4<\/jats:sub>), are used globally in menopausal hormone therapy. Although the older progestins medroxyprogesterone acetate (MPA) and norethisterone (NET) have been implicated in increased breast cancer risk, little is known regarding newer progestins, and no significant risk has been associated with P<jats:sub>4<\/jats:sub>. Considering that breast cancer is the leading cause of mortality in women, establishing which progestins increase breast cancer incidence and elucidating the underlying mechanisms is a global priority. We showed for the first time that the newer-generation progestin drospirenone (DRSP) is the least potent progestin in terms of proliferation of the estrogen-responsive MCF-7 BUS breast cancer cell line, while NET and P<jats:sub>4<\/jats:sub> have similar potencies to estradiol (E<jats:sub>2<\/jats:sub>), the known driver of breast cancer cell proliferation. Notably, MPA, the progestin most frequently associated with increased breast cancer risk, was significantly more potent than E<jats:sub>2<\/jats:sub>. While all the progestogens enhanced the anchorage-independent growth of the MCF-7 BUS cell line, MPA promoted a greater number of colonies than P<jats:sub>4<\/jats:sub>, NET or DRSP. None of the progestogens inhibited E<jats:sub>2<\/jats:sub>-induced proliferation and anchorage-independent growth. We also showed that under non-estrogenic conditions, MPA and NET, unlike P<jats:sub>4<\/jats:sub> and DRSP, increased the expression of the estrogen receptor (ER) target gene, <jats:italic>cathepsin D, via<\/jats:italic> a mechanism requiring the co-recruitment of ER\u03b1 and the progesterone receptor (PR) to the promoter region. In contrast, all progestogens promoted the association of the PR and ER\u03b1 on the promoter of the PR target gene, <jats:italic>MYC<\/jats:italic>, thereby increasing its expression under non-estrogenic and estrogenic conditions. These results suggest that progestins differentially regulate the way the PR and ER converge to modulate the expression of PR and ER-regulated genes. Our novel findings indicating similarities and differences between P<jats:sub>4<\/jats:sub> and the progestins, emphasize the importance of comparatively investigating effects of individual progestins rather than grouping them as a class. Further studies are required to underpin the clinical relevance of PR\/ER\u03b1 crosstalk in response to different progestins in both normal and malignant breast tissue, to either confirm or refute their suitability in combination therapy for ER-positive breast cancer.<\/jats:p>","DOI":"10.3389\/fendo.2022.959396","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:43:50Z","timestamp":1663224230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Upregulation of an estrogen receptor-regulated gene by first generation progestins requires both the progesterone receptor and estrogen receptor alpha"],"prefix":"10.3389","volume":"13","author":[{"given":"Meghan S.","family":"Perkins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Louw-du Toit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mishkah","family":"Simons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donita","family":"Africander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2004.01.001","article-title":"Pharmacological profile of progestins","volume":"47","author":"Sitruk-Ware","year":"2004","journal-title":"Maturitas"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.03.001","article-title":"Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception","volume":"76","author":"Africander","year":"2011","journal-title":"Steroids"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2010.04.004","article-title":"The use of newer progestins for contraception","volume":"82","author":"Sitruk-Ware","year":"2010","journal-title":"Contraception"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.maturitas.2003.09.014","article-title":"Classification and pharmacology of progestins","volume":"46","author":"Schindler","year":"2003","journal-title":"Maturitas"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.07.063","article-title":"Comparing the androgenic and estrogenic properties of progestins used in contraception and hormone therapy","volume":"491","author":"Louw-du Toit","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2014.05.007","article-title":"A comparative study of the androgenic properties of progesterone and the progestins, medroxyprogesterone acetate (MPA) and norethisterone acetate (NET-a)","volume":"143","author":"Africander","year":"2014","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1210\/er.2012-1008","article-title":"Progestogens used in postmenopausal hormone therapy: Differences in their pharmacological properties, intracellular actions, and clinical effects","volume":"34","author":"Stanczyk","year":"2013","journal-title":"Endocr Rev"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)14065-2","article-title":"Breast cancer and hormone replacement therapy in the million women study","volume":"362","year":"2003","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.3.321","article-title":"Risks and benefits of estrogen plus progestin in healthy postmenopausal women","volume":"288","year":"2002","journal-title":"J Am Med Assoc"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-007-9523-x","article-title":"Unequal risks for breast cancer associated with different hormone replacement therapies: Results from the E3N cohort study","volume":"107","author":"Fournier","year":"2008","journal-title":"Breast Cancer Res Treat"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.cd004143.pub4","article-title":"Long term hormone therapy for perimenopausal and postmenopausal women","volume":"7","author":"Marjoribanks","year":"2012","journal-title":"Cochrane Database Systematic Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31709-X","article-title":"Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence","volume":"394","year":"2019","journal-title":"Lancet"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1530\/ERC-16-0427","article-title":"Pushing estrogen receptor around in breast cancer","volume":"23","author":"Lim","year":"2016","journal-title":"Endocr Relat Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.coemr.2020.10.001","article-title":"Progestins in menopausal hormone therapy and breast cancer risk: The debate continues","volume":"15","author":"Africander","year":"2020","journal-title":"Curr Opin Endocr Metab Res"},{"key":"B15","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1210\/er.2017-00103","article-title":"Hormonal contraception and HIV-1 acquisition: Biological mechanisms","volume":"39","author":"Hapgood","year":"2018","journal-title":"Endocr Rev"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.168640","article-title":"Predicting response to endocrine therapy in human breast cancer: A hypothesis","volume":"189","author":"Horwitz","year":"1975","journal-title":"Sci (80- )"},{"key":"B17","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/nrc.2016.116","article-title":"Deciphering the divergent roles of progestogens in breast cancer","volume":"17","author":"Carroll","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1530\/JME-20-0104","article-title":"Progesterone and progesterone receptors in breast cancer: Past, present, future","volume":"65","author":"Horwitz","year":"2020","journal-title":"J Mol Endocrinol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2217\/17455057.4.2.151","article-title":"Progesterone and breast cancer","volume":"4","author":"Lange","year":"2008","journal-title":"Women\u2019s Heal"},{"key":"B20","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1530\/ERC-11-0378","article-title":"Antiprogestins in breast cancer treatment: Are we ready","volume":"19","author":"Lanari","year":"2012","journal-title":"Endocr Relat Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0141","article-title":"Breast cancer patients with progesterone receptor PR-A-Rich tumors have poorer disease-free survival rates","volume":"10","author":"Hopp","year":"2004","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1023\/B:BREA.0000014041.58977.80","article-title":"Effect of progesterone receptor a predominance on breast cancer cell migration into bone marrow fibroblasts","volume":"83","author":"McGowan","year":"2004","journal-title":"Breast Cancer Res Treat"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-10-2950","article-title":"Progesterone receptor isoform-specific promoter methylation: Association of PRA promoter methylation with worse outcome in breast cancer patients","volume":"17","author":"Pathiraja","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3290","article-title":"Estrogen receptor alpha mediates progestin-induced mammary tumor growth by interacting with progesterone receptors at the cyclin D1\/MYC promoters","volume":"72","author":"Giulianelli","year":"2012","journal-title":"Cancer Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.579","article-title":"Progesterone receptor-b enhances estrogen responsiveness of breast cancer cells via scaffolding PELP1-and estrogen receptor-containing transcription complexes","volume":"34","author":"Daniel","year":"2015","journal-title":"Oncogene"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5082","article-title":"Role of the short isoform of the progesterone receptor in breast cancer cell invasiveness at estrogen and progesterone levels in the pre- and post-menopausal ranges","volume":"6","author":"McFall","year":"2015","journal-title":"Oncotarget"},{"key":"B27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1530\/JME-14-0252","article-title":"Progesterone action in breast, uterine, and ovarian cancers","volume":"54","author":"Diep","year":"2015","journal-title":"J Mol Endocrinol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/nature14583","article-title":"Progesterone receptor modulates ER\u03b1 action in breast cancer","volume":"523","author":"Mohammed","year":"2015","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/sciadv.1501924","article-title":"Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors in breast cancer","volume":"2","author":"Singhal","year":"2016","journal-title":"Sci Adv"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.7.2008","article-title":"Activation of the Src\/p21(ras)\/Erk pathway by progesterone receptor via cross-talk with estrogen receptor","volume":"17","author":"Migliaccio","year":"1998","journal-title":"EMBO J"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3541","article-title":"Breast cancer suppression by progesterone receptors is mediated by their modulation of estrogen receptors and RNA polymerase III","volume":"77","author":"Finlay-Schultz","year":"2017","journal-title":"Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21378","article-title":"Progesterone receptor isoforms, agonists and antagonists differentially reprogram estrogen signaling","volume":"9","author":"Singhal","year":"2018","journal-title":"Oncotarget"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)05352-5","article-title":"The menopause","volume":"353","author":"Greendale","year":"1999","journal-title":"Lancet"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1525","article-title":"Involvement of up-regulation of 17\u03b2-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers","volume":"94","author":"Miyoshi","year":"2001","journal-title":"Int J Cancer"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.4.5047","article-title":"Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor","volume":"138","author":"Szelei","year":"1997","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jsbmb.2017.07.022","article-title":"A comparative characterization of estrogens used in hormone therapy via estrogen receptor (ER)-\u03b1 and -\u03b2","volume":"174","author":"Perkins","year":"2017","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pgen.1000922","article-title":"Activation of estrogen-responsive genes does not require their nuclear co-localization","volume":"6","author":"Kocanova","year":"2010","journal-title":"PLoS Genet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.076","article-title":"Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells","volume":"345","author":"Dieudonne","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021353","article-title":"Sex steroid hormone receptors in human thymoma","volume":"88","author":"Ishibashi","year":"2003","journal-title":"J Clin Endocrinol Metab"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Oxford Univ Press"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.587311","article-title":"Medroxyprogesterone acetate differentially regulates interleukin (IL)-12 and IL-10 in a human ectocervical epithelial cell line in a glucocorticoid receptor (GR)-dependent manner","volume":"289","author":"Louw-du Toit","year":"2014","journal-title":"J Biol Chem"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103339200","article-title":"Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer elements","volume":"276","author":"Castro-Rivera","year":"2001","journal-title":"J Biol Chem"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00188-4","article-title":"Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription","volume":"103","author":"Shang","year":"2000","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2004.09.005","article-title":"Not all progestins are the same: implications for usage","volume":"25","author":"Hapgood","year":"2004","journal-title":"Trends Pharmacol Sci"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1530\/JME-18-0094","article-title":"Hormone therapy and breast cancer: Emerging steroid receptor mechanisms","volume":"61","author":"Perkins","year":"2018","journal-title":"J Mol Endocrinol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-7824(97)00174-1","article-title":"In vivo conversion of norethisterone and norethisterone acetate to ethinyl etradiol in postmenopausal women","volume":"56","author":"Kuhnz","year":"1997","journal-title":"Contraception"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0096497","article-title":"The injectable-only contraceptive medroxyprogesterone acetate, unlike norethisterone acetate and progesterone, regulates inflammatory genes in endocervical cells via the glucocorticoid receptor","volume":"9","author":"Govender","year":"2014","journal-title":"PLoS One"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.steroids.2022.108998","article-title":"Differential off-target glucocorticoid activity of progestins used in endocrine therapy","volume":"182","author":"Komane","year":"2022","journal-title":"Steroids"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.100","article-title":"A direct comparison of the transcriptional activities of progestins used in contraception and menopausal hormone therapy via the mineralocorticoid receptor","volume":"526","author":"Louw-du Toit","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.95103844","article-title":"The e-screen assay: A comparison of different MCF7 cell stocks","volume":"103","author":"Villalobos","year":"1995","journal-title":"Environ Health Perspect"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12672-020-00379-1","article-title":"Progesterone and breast cancer: an NCI workshop report","volume":"11","author":"Sathyamoorthy","year":"2020","journal-title":"Horm Cancer"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.139","article-title":"Anchorage-independent cell growth signature identifies tumors with metastatic potential","volume":"28","author":"Mori","year":"2009","journal-title":"Oncogene"},{"key":"B53","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.steroids.2016.09.004","article-title":"Progesterone induces progesterone receptor gene (PGR) expression via rapid activation of protein kinase pathways required for cooperative estrogen receptor alpha (ER) and progesterone receptor (PR) genomic action at ER\/PR target genes","volume":"114","author":"Diep","year":"2016","journal-title":"Steroids"},{"key":"B54","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3322\/caac.21262","article-title":"Global cancer statistics, 2012","volume":"65","author":"Torre","year":"2015","journal-title":"CA Cancer J Clin"},{"key":"B55","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21332","article-title":"Cancer statistics, 2016","volume":"66","author":"Siegel","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2003.09.019","article-title":"Differential effects of progestogens on breast cancer cell lines","volume":"46","author":"Franke","year":"2003","journal-title":"Maturitas"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(95)00215-4","article-title":"Effects of two classes of progestagens, pregnane and 19-nortestosterone derivatives, on cell growth of human breast tumor cells: I","volume":"55","author":"Schoonen","year":"1995","journal-title":"MCF-7 Cell lines. J Steroid Biochem Mol Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/0960-0760(94)90170-8","article-title":"Inhibition by nomegestrol acetate and other synthetic progestins on proliferation and progesterone receptor content of T47-d human breast cancer cells","volume":"50","author":"Botella","year":"1994","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15252\/emmm.202114314","article-title":"Contraceptive progestins with androgenic properties stimulate breast epithelial cell proliferation","volume":"13","author":"Shamseddin","year":"2021","journal-title":"EMBO Mol Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-005-7726-6","article-title":"Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75","volume":"94","author":"Carvajal","year":"2005","journal-title":"Breast Cancer Res Treat"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/1414-431X20175612","article-title":"Estrogen and progesterone promote breast cancer cell proliferation by inducing cyclin G1 expression","volume":"51","author":"Tian","year":"2018","journal-title":"Braz J Med Biol Res"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1103","article-title":"Progestin-dependent progression of human breast tumor xenografts: A novel model for evaluating antitumor therapeutics","volume":"67","author":"Liang","year":"2007","journal-title":"Cancer Res"},{"key":"B64","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1023\/a:1007081021483","article-title":"Bcl-2, survivin and variant CD44 v7-v10 are downregulated and p53 is upregulated in breast cancer cells by progesterone: Inhibition of cell growth and induction of apoptosis","volume":"202","author":"Formby","year":"1999","journal-title":"Mol Cell Biochem"},{"key":"B65","article-title":"Growth inhibition and increase of insulin receptors in antiestrogen-resistant T47Dco human breast cancer cells by progestins: Implications for endocrine therapies","volume":"45","author":"Horwitz","year":"1985","journal-title":"Cancer Res"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002790","article-title":"Extra-nuclear signaling of progesterone receptor to breast cancer cell movement and invasion through the actin cytoskeleton","volume":"3","author":"Fu","year":"2008","journal-title":"PLoS One"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1210\/mend.12.9.0159","article-title":"Upstream stimulatory factors mediate estrogen receptor activation of the cathepsin d promoter","volume":"12","author":"Xing","year":"1998","journal-title":"Mol Endocrinol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1210\/mend.8.6.7935485","article-title":"Characterization of the proximal estrogen-responsive element of human cathepsin d gene","volume":"8","author":"Augereau","year":"1994","journal-title":"Mol Endocrinol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5331.1508","article-title":"Differential ligand activation of estrogen receptors ER\u03b1 and ER\u03b2 at AP1 sites","volume":"277","author":"Paech","year":"1997","journal-title":"Science"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/s0960-0760(00)00108-4","article-title":"Estrogen receptor pathways to AP-1","volume":"74","author":"Kushner","year":"2000","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10696","article-title":"Progesterone regulates transcription of the p21(WAF1) cyclin-dependent kinase inhibitor gene through Sp1 and CBP\/p300","volume":"273","author":"Owen","year":"1998","journal-title":"J Biol Chem"},{"key":"B72","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1677\/jme.1.01541","article-title":"Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors \u03b1 and \u03b2 by coactivators and corepressors","volume":"33","author":"Klinge","year":"2004","journal-title":"J Mol Endocrinol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.14.2905","article-title":"Estrogen receptor interaction with estrogen response elements","volume":"29","author":"Klinge","year":"2001","journal-title":"Nucleic Acids Res"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1677\/erc.0.0070143","article-title":"C- myc in breast cancer","volume":"7","author":"Liao","year":"2000","journal-title":"Endocr Relat Cancer"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, metabolism, and cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discovery 1"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1515\/HMBCI.2011.008","article-title":"Effect of drospirenone on proliferation of human benign and cancerous epithelial breast cells","volume":"6","author":"Seeger","year":"2011","journal-title":"Horm Mol Biol Clin Investig"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1080\/cmt.6.3.221.227","article-title":"Comparison of the proliferative effects of estradiol and conjugated equine estrogens on human breast cancer cells and impact of continuous combined progestogen addition","volume":"6","author":"Mueck","year":"2003","journal-title":"Climacteric"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2012.09.038","article-title":"Effects of estradiol and progestogens on human breast cells: Regulation ofsex steroid receptors","volume":"52","author":"Chen","year":"2013","journal-title":"Taiwan J Obstet Gynecol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1055\/s-2005-870306","article-title":"Dose\u2013dependent changes of the ratio of apoptosis to proliferation by norethisterone and medroxyproges\u2013 terone acetate in human breast epithelial cells","volume":"37","author":"Seeger","year":"2005","journal-title":"Horm Metab Res"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1097\/gme.0b013e3181d3dd0c","article-title":"Synthetic progestins induce growth and metastasis of BT-474 human breast cancer xenografts in nude mice","volume":"17","author":"Liang","year":"2010","journal-title":"Menopause"},{"key":"B81","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jsbmb.2019.105548","article-title":"Anti-proliferative transcriptional effects of medroxyprogesterone acetate in estrogen receptor positive breast cancer cells are predominantly mediated by the progesterone receptor","volume":"1055","author":"Moore","year":"2020","journal-title":"J Steroid Biochem Mol Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.959396\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T06:43:54Z","timestamp":1663224234000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.959396\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,15]]},"references-count":81,"alternative-id":["10.3389\/fendo.2022.959396"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.959396","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,15]]},"article-number":"959396"}}