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Mammary Gland Morphological and Gene Expression Changes Underlying Pregnancy Protection of Breast Cancer Tumorigenesis

ABSTRACT: Pregnancy has been shown to decrease the risk of mammary carcinogenesis in human rretrospective epidemiological studies. In rodents, pregnancy prior to carcinogen administration or after carcinogen challenge has also been shown to reduce the incidence of palpable carcinomas. In this study our objective to determine the underlying genomic signature of the pregnancy and reproductive hormones on the mammary gland that contribute to the protection against mammary gland carcinogenesis. We used the rat microarray technology to observe total transcriptome changes after the pregnancy and exogenous reproductive hormone stimulation of the mammary gland.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE32125 | GEO | 2011/09/15

SECONDARY ACCESSION(S): PRJNA147429

REPOSITORIES: GEO

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Mammary Gland Morphological and Gene Expression Changes Underlying Pregnancy Protection of Breast Cancer Tumorigenesis

Project description:Pregnancy has been shown to decrease the risk of mammary carcinogenesis in human rretrospective epidemiological studies. In rodents, pregnancy prior to carcinogen administration or after carcinogen challenge has also been shown to reduce the incidence of palpable carcinomas. In this study our objective to determine the underlying genomic signature of the pregnancy and reproductive hormones on the mammary gland that contribute to the protection against mammary gland carcinogenesis. We used the rat microarray technology to observe total transcriptome changes after the pregnancy and exogenous reproductive hormone stimulation of the mammary gland. Fifteen 3 month old post-pubertal virgin Lewis rats were randomly assigned to three groups (5 rats per group): control (C), pregnancy (P) and hormone treatment (H). The P group animals had a full-term pregnancy (21-23 days) and rats in the group H were implanted subcutaneously on the dorsal midline with two silastic capsules [(0.078 inch inner diameter, 0.125 inch outer diameter) x 2 cm long; Dow Corning, Midland, MI) filled separately with 100 μg ethynyl estradiol (Sigma, St. Louis, MO) packed in a cellulose matrix (Sigma) and 30 mg of megesterol acetate (Sigma) for 21 days. The control animals had neither the hormone treatment nor being pregnant. The animals in C and P groups were also implanted with sham capsules filled with cellulose matrix only. The capsules were surgically implanted at the beginning of the experiment and removed from all animals after 21 days except that the capsules were removed from the P group following parturition (21-23 days). The delivered pups in the P group were euthanized within 4-6 hours of delivery to avoid suckling. After the removal of capsules all groups were rested a total of ~49 days before euthanasia. All animals were euthanized during metestrus stage, determined by vaginal cytology and total RNA was extracted from the mammary gland tissues using Trizol reagent.

2011-09-14 | E-GEOD-32125 | biostudies-arrayexpress

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Transcription profiling of mouse mammary gland responses to estrogen and progesterone

Project description:Epidemiological studies have shown that a full-term pregnancy at early age can decrease the breast cancer risk up to one-half. Pregnancy has been shown to prevent carcinogen-induced mammary tumors in rodents as well. The protective effect of pregnancy can be mimicked by administration of estrogen and progesterone to nulliparous rodents in amounts that are similar to those during pregnancy and alters responsiveness of p53 to DNA damage. Ovariectomized mice were treated with estrogen (E), progesterone (P), both estrogen and progesterone (E + P), or vehicle (V) alone and global expression profiles was analyzed to identify the mechanisms by which estrogen and progesterone combine to sensitize p53 function. Experiment Overall Design: Twenty ovariectomized animals were used for examine transcriptional effects of hormones by microarray. The hormones were administered by daily i.p. injection for 4 days.Treatment groups included: 4 animals receiving 2ug 17-beta-estrogen (E), 4 animals receiving 1mg progesterone (P), 5 animals receiving both estrogen and progesterone (E+P) and 4 animals receiving 100ul sesame oil (V). Epithelial-free fat pads from 3 animals receiving E+P were also analyzed to distinguish responses to E+P in the stroma (E+P CFP). Lymph nodes were removed from mammary glands at the time of collection.

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An epigenetic memory of pregnancy in the mouse mammary gland

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Expression data from mammary gland during pregnancy and lactation of CBA/CaH, QSi5 and Advanced Intercross Line (AIL; CBA/CaH X QSi5, the 14th generation)

Project description:Previously we have shown significant differences in lactation performance, mammary gland histology and expression profiles of mammary transcriptome during peak-lactation (lactation day 9; L9) between the ordinary CBA/CaH (CBA) and the superior QSi5 strains of mice. In the present study, we compared mammary gland histology between CBA and QSi5 at mid-pregnancy (pregnancy day 12; P12). We assessed lactation performance during the first 8 days of lactation of the 13th - 14th generation of the Advanced Intercross Line (AIL) (CBA X QSi5) mice. We utilized an integrative approach to analyzing mammary microarray expression profiles of CBA and QSi5 at P12 and CBA, AIL and QSi5 at L9. The inguinal mammary glands of CBA/CaH and QSi5 during mid-pregnancy (Pregnancy day 12; P12), and the glands of CBA/CaH, AIL and QSi5 during peak lactation (Lactation day 9; L9) were collected and total RNA was extracted for Affymetrix microarray (mouse genome 430 2) assay

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Pregnancy-associated alterations in DNA methylation patterns of mammary epithelial stem cells [inhibitor study]

Project description:Mammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. To explore the role of DNA methylation in luminal cell differentiation and pregnancy-induced changes, we determined the genome-wide DNA methylation and gene expression profiles of mammary epithelial stem, luminal progenitor, and mature luminal cells at different reproductive stages. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell type and reproductive stage-specific changes in molecular signatures. We also identified p27 and TGFβ signaling as key regulators of luminal progenitor cell proliferation based on their expression patterns and by the use of explant cultures. Our results suggest relatively minor changes in DNA methylation during luminal cell differentiation as compared to the significant effects of pregnancy on mammary epithelial stem cells. Mammary glands were collected from mice treated with DNA methylation inhibitor 5-azacytidine (AzaC) and histone deacetylase inhibitor valproic acid (VPA) at non-pregnant and pregnant stages for RNA extraction and hybridization on Affymetrix microarrays.

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