Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland.

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.

[1]  O. Haas,et al.  Felix Mitelman: Database of chromosome aberrations in cancer , 2002, Human Genetics.

[2]  Leif E. Peterson,et al.  Short-term exposure to estrogen and progesterone induces partial protection against N-nitroso-N-methylurea-induced mammary tumorigenesis in Wistar--Furth rats. , 2001, Cancer letters.

[3]  A. Leutz,et al.  Chromatin remodeling in development and differentiation. , 2001, Current opinion in genetics & development.

[4]  D. Zink,et al.  Chromodomains are protein–RNA interaction modules , 2000, Nature.

[5]  A. Wolffe,et al.  Co-repressor complexes and remodelling chromatin for repression. , 2000, Biochemical Society transactions.

[6]  B. Weber,et al.  Genetic and hormonal risk factors in breast cancer. , 2000, Journal of the National Cancer Institute.

[7]  K. Tsuchida,et al.  Expression of a TGF-β1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines , 2000 .

[8]  J. Russo,et al.  Chapter 1: Developmental, Cellular, and Molecular Basis of Human Breast Cancer , 2000 .

[9]  E. Moss,et al.  Non-coding RNAs: Lightning strikes twice , 2000, Current Biology.

[10]  Mike Clarke,et al.  UK and USA breast cancer deaths down 25% in year 2000 at ages 20–69 years , 2000, The Lancet.

[11]  J. Russo,et al.  Developmental, cellular, and molecular basis of human breast cancer. , 2000, Journal of the National Cancer Institute. Monographs.

[12]  Y. C. Kim,et al.  Regulation of stearoyl-CoA desaturase genes: role in cellular metabolism and preadipocyte differentiation. , 1999, Biochemical and biophysical research communications.

[13]  A. Wolffe,et al.  Functional Analysis of the SIN3-Histone Deacetylase RPD3-RbAp48-Histone H4 Connection in the XenopusOocyte , 1999, Molecular and Cellular Biology.

[14]  A. Bird,et al.  Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. , 1999, Genes & development.

[15]  D. A. White,et al.  Maternal histone deacetylase is accumulated in the nuclei of Xenopus oocytes as protein complexes with potential enzyme activity. , 1999, Journal of cell science.

[16]  D. Medina,et al.  Chemical carcinogen-induced tumorigenesis in parous, involuted mouse mammary glands. , 1999, Journal of the National Cancer Institute.

[17]  R. Yarden,et al.  BRCA1 interacts with components of the histone deacetylase complex. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Neil J McKenna,et al.  A Steroid Receptor Coactivator, SRA, Functions as an RNA and Is Present in an SRC-1 Complex , 1999, Cell.

[19]  H. Gardner,et al.  Mammary gland development, reproductive history, and breast cancer risk. , 1999, Cancer research.

[20]  R. Guzman,et al.  Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  P. Brown,et al.  Combining SSH and cDNA microarrays for rapid identification of differentially expressed genes. , 1999, Nucleic acids research.

[22]  Zhaoyi Wang,et al.  Induction of Rb-associated Protein (RbAp46) by Wilms’ Tumor Suppressor WT1 Mediates Growth Inhibition* , 1998, The Journal of Biological Chemistry.

[23]  D. Kellogg,et al.  Control of mitotic events by the Cdc42 GTPase, the Clb2 cyclin and a member of the PAK kinase family , 1998, Current Biology.

[24]  B. O’Malley,et al.  Hormone-induced refractoriness to mammary carcinogenesis in Wistar-Furth rats. , 1998, Carcinogenesis.

[25]  L. Hennighausen,et al.  Think globally, act locally: the making of a mouse mammary gland. , 1998, Genes & development.

[26]  D J Lipman,et al.  Making (anti)sense of non-coding sequence conservation. , 1997, Nucleic acids research.

[27]  Oliver D. von Stein,et al.  A high throughput screening for rarely transcribed differentially expressed genes , 1997, Nucleic Acids Res..

[28]  M. Kasuga,et al.  Interaction of Nck-associated protein 1 with activated GTP-binding protein Rac. , 1997, The Biochemical journal.

[29]  J. Russo,et al.  Mammary gland neoplasia in long-term rodent studies. , 1996, Environmental health perspectives.

[30]  F. Talamantes,et al.  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? , 1995, Carcinogenesis.

[31]  Yue Qian,et al.  Dual Retinoblastoma-binding Proteins with Properties Related to a Negative Regulator of Ras in Yeast (*) , 1995, The Journal of Biological Chemistry.

[32]  B Rosner,et al.  Reproductive risk factors in a prospective study of breast cancer: the Nurses' Health Study. , 1994, American journal of epidemiology.

[33]  Y. Qian,et al.  A retinoblastoma-binding protein related to a negative regulator of Ras in yeast , 1993, Nature.

[34]  J. Russo,et al.  Comparative study of the influence of pregnancy and hormonal treatment on mammary carcinogenesis. , 1991, British Journal of Cancer.

[35]  J. Kelsey,et al.  The epidemiology of breast cancer. , 1991, CA: a cancer journal for clinicians.

[36]  J. Russo,et al.  Effect of human chorionic gonadotropin on mammary gland differentiation and carcinogenesis. , 1990, Carcinogenesis.

[37]  J. Russo,et al.  Human chorionic gonadotropin and rat mammary cancer prevention. , 1990, Journal of the National Cancer Institute.

[38]  D. Sinha,et al.  Prevention of mammary carcinogenesis in rats by pregnancy: effect of full-term and interrupted pregnancy. , 1988, British Journal of Cancer.

[39]  M. Juliana,et al.  Short-term hormone treatment as a chemopreventive method against mammary cancer initiation in rats. , 1988, Anticancer research.

[40]  J. Russo,et al.  Biological and molecular bases of mammary carcinogenesis. , 1987, Laboratory investigation; a journal of technical methods and pathology.

[41]  P. Strittmatter,et al.  Construction and sequence of cDNA for rat liver stearyl coenzyme A desaturase. , 1986, The Journal of biological chemistry.

[42]  C. Grubbs,et al.  Chemoprevention of N-Nitroso-N-methylurea-Induced Mammary Cancers by Pretreatment with 17β-Estradiol and Progesterone , 1985 .

[43]  J. Williams,et al.  Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. , 1983, Developmental biology.

[44]  C. Grubbs,et al.  Mammary carcinogenesis in rats in relation to age at time of N-nitroso-N-methylurea administration. , 1983, Journal of the National Cancer Institute.

[45]  L. Tay,et al.  Formation and removal of 7,12-dimethylbenz[a]anthracene--nucleic acid adducts in rat mammary epithelial cells with different susceptibility to carcinogenesis. , 1981, Carcinogenesis.

[46]  J. Russo,et al.  Susceptibility of the mammary gland to carcinogenesis. II. Pregnancy interruption as a risk factor in tumor incidence. , 1980, The American journal of pathology.

[47]  C. Lowe,et al.  Age at first birth and breast cancer risk. , 1970, Bulletin of the World Health Organization.

[48]  R. Moon.  Relationship between previous reproductive history and chemically induced mammary cancer in rats , 1969, International journal of cancer.

[49]  C. Huggins,et al.  Extinction of experimental mammary cancer. I. Estradiol-17beta and progesterone. , 1962, Proceedings of the National Academy of Sciences of the United States of America.