{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:31:11Z","timestamp":1791235871794,"version":"4.1.0"},"reference-count":52,"publisher":"The Endocrine Society","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2001,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.<\/jats:p>","DOI":"10.1210\/mend.15.11.0724","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:30:44Z","timestamp":1389202244000},"page":"1993-2009","source":"Crossref","is-referenced-by-count":95,"title":["Persistent Changes in Gene Expression Induced by Estrogen and Progesterone in the Rat Mammary Gland"],"prefix":"10.1210","volume":"15","author":[{"given":"Melanie R.","family":"Ginger","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3411"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Gonzalez-Rimbau","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3411"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P.","family":"Gay","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3411"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Rosen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030-3411"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071614211178500_R1","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1016\/S0140-6736(00)02277-7","article-title":"UK and USA breast cancer deaths down 25% in year 2000 at ages 20\u201369 years.","volume":"355","author":"Peto","year":"2000","journal-title":"Lancet"},{"key":"2020071614211178500_R2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/oxfordjournals.jncimonographs.a024241","article-title":"Developmental, cellular, and molecular basis of human breast cancer.","volume":"27","author":"Russo","year":"2000","journal-title":"J Natl Cancer Inst Monogr"},{"key":"2020071614211178500_R3","first-page":"1765","article-title":"Mammary gland development, reproductive history, and breast cancer risk.","volume":"59","author":"Chodosh","year":"1999","journal-title":"Cancer Res"},{"key":"2020071614211178500_R4","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1093\/jnci\/92.14.1126","article-title":"Genetic and hormonal risk factors in breast cancer.","volume":"92","author":"Martin","year":"2000","journal-title":"J Natl Cancer Inst"},{"key":"2020071614211178500_R5","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/oxfordjournals.aje.a117079","article-title":"Reproductive risk factors in a prospective study of breast cancer: the Nurses\u2019 Health Study.","volume":"139","author":"Rosner","year":"1994","journal-title":"Am J Epidemiol"},{"key":"2020071614211178500_R6","first-page":"209","article-title":"Age at first birth and breast cancer risk.","volume":"43","author":"MacMahon","year":"1970","journal-title":"Bull WHO"},{"key":"2020071614211178500_R7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3322\/canjclin.41.3.146","article-title":"The epidemiology of breast cancer.","volume":"41","author":"Kelsey","year":"1991","journal-title":"CA Cancer J Clin"},{"key":"2020071614211178500_R8","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1002\/ijc.2910040308","article-title":"Relationship between previous reproductive history and chemically induced mammary cancer in rats.","volume":"4","author":"Moon","year":"1969","journal-title":"Int J Cancer"},{"key":"2020071614211178500_R9","first-page":"497","article-title":"Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence.","volume":"100","author":"Russo","year":"1980","journal-title":"Am J Pathol"},{"key":"2020071614211178500_R10","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/bjc.1988.88","article-title":"Prevention of mammary carcinogenesis in rats by pregnancy: effect of full-term and interrupted pregnancy.","volume":"57","author":"Sinha","year":"1988","journal-title":"Br J Cancer"},{"key":"2020071614211178500_R11","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1093\/carcin\/19.9.1573","article-title":"Hormone-induced refractoriness to mammary carcinogenesis in Wistar-Furth rats.","volume":"19","author":"Sivaraman","year":"1998","journal-title":"Carcinogenesis"},{"key":"2020071614211178500_R12","first-page":"209","article-title":"Mammary carcinogenesis in rats in relation to age at time of N-nitroso-N-methylurea administration.","volume":"70","author":"Grubbs","year":"1983","journal-title":"J Natl Cancer Inst"},{"key":"2020071614211178500_R13","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/BF01833517","article-title":"Influence of age and parity on the development of the human breast.","volume":"23","author":"Russo","year":"1992","journal-title":"Breast Cancer Res Treat"},{"key":"2020071614211178500_R14","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1023\/A:1018770218022","article-title":"Role of hormones in mammary cancer initiation and progression.","volume":"3","author":"Russo","year":"1998","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"2020071614211178500_R15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1073\/pnas.48.3.379","article-title":"Extinction of experimental mammary cancer. I. Estradiol-17\u03b2 and progesterone.","volume":"48","author":"Huggins","year":"1962","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614211178500_R16","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/bjc.1991.335","article-title":"Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis.","volume":"64","author":"Russo","year":"1991","journal-title":"Br J Cancer"},{"key":"2020071614211178500_R17","first-page":"927","article-title":"Chemoprevention of N-nitroso-N-methylurea-induced mammary cancers by pretreatment with 17\u03b2-estradiol and progesterone.","volume":"74","author":"Grubbs","year":"1985","journal-title":"J Natl Cancer Inst"},{"key":"2020071614211178500_R18","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1093\/jnci\/82.15.1286","article-title":"Human chorionic gonadotropin and rat mammary cancer prevention.","volume":"82","author":"Russo","year":"1990","journal-title":"J Natl Cancer Inst"},{"key":"2020071614211178500_R19","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1093\/carcin\/11.10.1849","article-title":"Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis.","volume":"11","author":"Russo","year":"1990","journal-title":"Carcinogenesis"},{"key":"2020071614211178500_R20","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1093\/jnci\/91.11.967","article-title":"Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands.","volume":"91","author":"Medina","year":"1999","journal-title":"J Natl Cancer Inst"},{"key":"2020071614211178500_R21","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/carcin\/16.11.2847","article-title":"Refractoriness to mammary tumorigenesis in parous rats: is it caused by persistent changes in the hormonal environment or permanent biochemical alterations in the mammary epithelia?","volume":"16","author":"Thordarson","year":"1995","journal-title":"Carcinogenesis"},{"key":"2020071614211178500_R22","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1073\/pnas.96.5.2520","article-title":"Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy.","volume":"96","author":"Guzman","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614211178500_R23","first-page":"113","article-title":"Short-term hormone treatment as a chemopreventive method against mammary cancer initiation in rats.","volume":"8","author":"Grubbs","year":"1988","journal-title":"Anticancer Res"},{"key":"2020071614211178500_R24","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1101\/gad.12.4.449","article-title":"Think globally, act locally: the making of a mouse mammary gland.","volume":"12","author":"Hennighausen","year":"1998","journal-title":"Genes Dev"},{"key":"2020071614211178500_R25","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1289\/ehp.96104938","article-title":"Mammary gland neoplasia in long-term rodent studies.","volume":"104","author":"Russo","year":"1996","journal-title":"Environ Health Perspect"},{"key":"2020071614211178500_R26","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1093\/nar\/25.13.2598","article-title":"A high throughput screening for rarely transcribed differentially expressed genes.","volume":"25","author":"von Stein","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2020071614211178500_R27","doi-asserted-by":"crossref","first-page":"25507","DOI":"10.1074\/jbc.270.43.25507","article-title":"Dual retinoblastoma-binding proteins with properties related to a negative regulator of ras in yeast.","volume":"270","author":"Qian","year":"1995","journal-title":"J Biol Chem"},{"key":"2020071614211178500_R28","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1042\/bj3220873","article-title":"Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac.","volume":"322","author":"Kitamura","year":"1997","journal-title":"Biochem J"},{"key":"2020071614211178500_R29","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S0960-9822(07)00419-8","article-title":"Control of mitotic events by the cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family.","volume":"8","author":"Tjandra","year":"1998","journal-title":"Curr Biol"},{"key":"2020071614211178500_R30","doi-asserted-by":"crossref","first-page":"13230","DOI":"10.1016\/S0021-9258(18)69295-6","article-title":"Construction and sequence of cDNA for rat liver stearyl coenzyme A desaturase.","volume":"261","author":"Thiede","year":"1986","journal-title":"J Biol Chem"},{"key":"2020071614211178500_R31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/bbrc.1999.1704","article-title":"Regulation of stearyl-CoA desaturase genes: role in cellular metabolism and preadipocyte differentiation.","volume":"266","author":"Kim","year":"1999","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614211178500_R32","article-title":"Database of chromosome aberrations in cancer.","author":"Mitelman","year":"2001"},{"key":"2020071614211178500_R33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/BF02096299","article-title":"The mammary gland: a unique organ for the study of development and tumorigenesis.","volume":"1","author":"Medina","year":"1996","journal-title":"J Mammary Gland Biol Neoplasia"},{"key":"2020071614211178500_R34","first-page":"112","article-title":"Biological and molecular bases of mammary carcinogenesis.","volume":"57","author":"Russo","year":"1987","journal-title":"Lab Invest"},{"key":"2020071614211178500_R35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/BF01805718","article-title":"Differentiation of the mammary gland and susceptibility to carcinogenesis.","volume":"2","author":"Russo","year":"1982","journal-title":"Breast Cancer Res Treat"},{"key":"2020071614211178500_R36","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1093\/carcin\/2.12.1327","article-title":"Formation and removal of 7,12-dimethylbenz[a]anthracene-nucleic acid adducts in rat mammary epithelial cells with different susceptibility to carcinogenesis.","volume":"2","author":"Tay","year":"1981","journal-title":"Carcinogenesis"},{"key":"2020071614211178500_R37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0304-3835(01)00507-9","article-title":"Short-term exposure to estrogen and progesterone induces partial protection against N-nitroso-N-methylurea-induced mammary tumorigenesis in Wistar-Furth rats.","volume":"169","author":"Medina","year":"2001","journal-title":"Cancer Lett"},{"key":"2020071614211178500_R38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0959-437X(00)00175-1","article-title":"Chromatin remodeling in development and differentiation.","volume":"11","author":"Muller","year":"2001","journal-title":"Curr Opin Genet Dev"},{"key":"2020071614211178500_R39","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1093\/nar\/27.6.1517","article-title":"Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes.","volume":"27","author":"Yang","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"2020071614211178500_R40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0304-3835(00)00407-9","article-title":"Expression of a TGF-\u03b21 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines.","volume":"155","author":"Sumitomo","year":"2000","journal-title":"Cancer Lett"},{"key":"2020071614211178500_R41","doi-asserted-by":"crossref","first-page":"R436","DOI":"10.1016\/S0960-9822(00)00528-5","article-title":"Non-coding RNA\u2019s: lightning strikes twice","volume":"10","author":"Moss","year":"2000","journal-title":"Curr Biol"},{"key":"2020071614211178500_R42","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/35030169","article-title":"Chromodomains are protein-RNA interaction modules.","volume":"407","author":"Akhtar","year":"2000","journal-title":"Nature"},{"key":"2020071614211178500_R43","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0092-8674(00)80711-4","article-title":"A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex.","volume":"97","author":"Lanz","year":"1999","journal-title":"Cell"},{"key":"2020071614211178500_R44","doi-asserted-by":"crossref","first-page":"3580","DOI":"10.1093\/nar\/25.18.3580","article-title":"Making (anti)sense of non-coding sequence conservation.","volume":"25","author":"Lipman","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2020071614211178500_R45","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/364648a0","article-title":"A retinoblastoma-binding protein related to a negative regulator of Ras in yeast.","volume":"364","author":"Qian","year":"1993","journal-title":"Nature"},{"key":"2020071614211178500_R46","doi-asserted-by":"crossref","first-page":"27047","DOI":"10.1074\/jbc.273.42.27047","article-title":"Induction of Rb-associated protein (RbAp46) by Wilms\u2019 tumor suppressor WT1 mediates growth inhibition.","volume":"273","author":"Guan","year":"1998","journal-title":"J Biol Chem"},{"key":"2020071614211178500_R47","doi-asserted-by":"crossref","first-page":"4983","DOI":"10.1073\/pnas.96.9.4983","article-title":"BRCA1 interacts with components of the histone deacetylase complex.","volume":"96","author":"Yarden","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071614211178500_R48","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1242\/jcs.112.14.2441","article-title":"Maternal histone deacetylase is accumulated in the nuclei of Xenopus oocytes as protein complexes with potential enzyme activity.","volume":"112","author":"Ryan","year":"1999","journal-title":"J Cell Sci"},{"key":"2020071614211178500_R49","doi-asserted-by":"crossref","first-page":"5847","DOI":"10.1128\/MCB.19.9.5847","article-title":"Functional analysis of the SIN3-histone deacetylase RPD3-RbAp48-histone H4 connection in the Xenopus oocyte.","volume":"19","author":"Vermaak","year":"1999","journal-title":"Mol Cell Biol"},{"key":"2020071614211178500_R50","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1101\/gad.13.15.1924","article-title":"Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation.","volume":"13","author":"Zhang","year":"1999","journal-title":"Genes Dev"},{"key":"2020071614211178500_R51","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1042\/bst0280379","article-title":"Co-repressor complexes and remodelling chromatin for repression.","volume":"28","author":"Wolffe","year":"2000","journal-title":"Biochem Soc Trans"},{"key":"2020071614211178500_R52","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/0012-1606(83)90086-6","article-title":"Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis.","volume":"97","author":"Williams","year":"1983","journal-title":"Dev Biol"}],"container-title":["Molecular Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/15\/11\/1993\/8950247\/mend1993.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/mend\/article-pdf\/15\/11\/1993\/8950247\/mend1993.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:27:49Z","timestamp":1647908869000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/mend\/article\/15\/11\/1993\/2747941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,11,1]]},"references-count":52,"aliases":["10.1210\/me.15.11.1993"],"journal-issue":{"issue":"11","published-print":{"date-parts":[[2001,11,1]]}},"URL":"https:\/\/doi.org\/10.1210\/mend.15.11.0724","relation":{},"ISSN":["0888-8809","1944-9917"],"issn-type":[{"value":"0888-8809","type":"print"},{"value":"1944-9917","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,11,1]]}}}