Estrogen Induces Estrogen-related Receptor Gene Expression and Chromatin Structural Changes in Estrogen Receptor (ER)-positive and ER-negative Breast Cancer Cells*

http://www.jbc.org/cgi/content/abstract/M705937200v1

J. Biol. Chem., Vol. 283, Issue 11, 6752-6763, March 14, 2008

Peng Hu, H. Karimi Kinyamu, Liangli Wang, Jessica Martin, Trevor K. Archer, and Christina Teng¹

From the Gene Regulation Section, Laboratory of Reproductive and Developmental Toxicology and Chromatin and Gene Expression Section, Laboratory of Molecular Carcinogenesis, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709

Estrogen-related receptor  (ERR) alpha, a member of the nuclear receptor superfamily, is closely related to the estrogen receptors (ER alpha and ERR alpha). The ERR alpha gene is estrogen-responsive in several mouse tissues and cell lines, and a multiple hormone-response element (MHRE) in the promoter is an important regulatory region for estrogen-induced ERR alpha gene expression. ERR alpha was recently shown to be a negative prognostic factor for breast cancer survival, with its expression being highest in cancer cells lacking functional ER. The contribution of ERR alpha in breast cancer progression remains unknown but may have important clinical implications. In this study, we investigated ERR alpha gene expression and chromatin structural changes under the influence of 17?-estradiol in both ER-positive MCF-7 and ER-negative SKBR3 breast cancer cells. We mapped the nucleosome positions of the ERR alpha promoter around the MHRE region and found that the MHRE resides within a single nucleosome. Local chromatin structure of the MHRE exhibited increased restriction enzyme hypersensitivity and enhanced histone H3 and H4 acetylation upon estrogen treatment. Interestingly, estrogen-induced chromatin structural changes could be repressed by estrogen antagonist ICI 182 780 in MCF-7 cells yet were enhanced in SKBR3 cells. We demonstrated, using chromatin immunoprecipitation assays, that 17 beta-estradiol induces ERR alpha gene expression in MCF-7 cells through active recruitment of co-activators and release of co-repressors when ERR and AP1 bind and ER alpha is tethered to the MHRE. We also found that this estrogen effect requires the MAPK signaling pathway in both cell lines.

Link

http://bmj.com/cgi/content/short/335/7623/740-a?etoc

Scientists welcome ruling on patent on breast cancer gene

but will it still cost an arm and a leg ?

http://www.jbc.org/cgi/content/abstract/M704418200v1?papetoc

Anti-hepatitis C virus activity of tamoxifen reveals the functional association of estrogen receptor with viral RNA polymerase NS5B

J. Biol. Chem, 10.1074/jbc.M704418200

[[...We found that tamoxifen (TAM) suppressed HCV genome replication...]]

Evaluation of the effect of obesity on selected haemostatic and fibrinolytic parameters in peri- and postmenopausal women

Polac I, Stetkiewicz T, Stachowiak G, Jedrzejczyk S, Pertynski T, Pakalski A, Kowalska E.
Klinika Ginekologii i Chorob Menopauzy Instytutu Centrum Zdrowia Matki Polki w Lodzi.

Localization of adipose tissue influence on obesity-dependent diseases. In obese people many abnormalities are observed connected with coagulation factors and fibrinolysis. We studied 47 peri- and postmenopausal female patients, who were operated on for benign changes within the pelvis minor. The patients were divided according to BMI (group I--BMI <25 kg/m2, group II--BMI > 29 kg/m2). In obese women lower SHBG concentration, higher insulin and glucose fasting blood levels, higher LDL, higher total fatty tissue content, higher fibrinogen level and elevated PAI-1 activity were found. A positive correlation between area under insulin curve and PAI-1 activity and a negative correlation between fasting insulin levels and tPA were also observed.

Based on the studies performed it can be said that:

1. Fatty tissue content in postmenopausal women exerts an influence on PAI-1 activity.
2. Obesity influences coagulation and fibrinolysis system in peri- and postmenopausal women.
3. Carbohydrate metabolism disturbances have influence on PAI-1 activity in peri- and postmenopausal women.

PMID: 12474565 [PubMed - indexed for MEDLINE]

Pol Merkur Lekarski. 2002 Sep;13(75):182-4

[I edited the date of first posting to bring this one to the top of the blog ~ originally 2nd January 2006]
can be edited under 'advanced properties' time stamp

Metabolic Targeting as an Anticancer Strategy: Dawn of a New Era?

James G. Pan1* and Tak W. Mak2*

1Campbell Family Institute for Breast Cancer Research, University Health Network TMDT East Tower, MaRs Centre, 101 College Street, 5-705, Toronto, ON M5G 1L7, Canada.
2Campbell Family Institute for Breast Cancer Research, University Health Network and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, ON, M5G 2C1, Canada.

http://dx.doi.org/10.1126/stke.3812007pe14

http://www.signaling-gateway.org/update/updates/200705/nrm2168.html

Gain-of-function mutations in the tumor suppressor p53 promote oncogenesis by interfering with DNA repair.

[[...The authors argue that "a novel gain-of-function of common p53 cancer mutants in disrupting critical DNA DSB damage responses will have significant implications on the therapeutic interventions for human cancers that express p53 cancer mutants."...]]

http://carcin.oxfordjournals.org/cgi/content/short/bgi226v1

Lymphocytes of BRCA1 and BRCA2 germ-line mutation carriers, with or without breast cancer, are not abnormally sensitive to the chromosome damaging effect of moderate folate deficiency

Sasja Beetstra 1, 2, Carolyn Salisbury 1, Julie Turner 1, Meryl Altree 3, Ross McKinnon 2, Graeme Suthers 3, 4 and Michael Fenech 1, *

1 CSIRO Human Nutrition, PO Box 10041, Gouger Street, Adelaide BC 5000, SA, Australia, 2 Sansom Research Institute, The University of South Australia, Adelaide 5000, SA, Australia, 3 Familial Cancer Unit, SA Clinical Genetics Service, Children's, Youth and Women's Health Service, North Adelaide 5006, SA, Australia 4 Department of Pediatrics, University of Adelaide, Adelaide 5003, SA, Australia

Mutations in BRCA1 and BRCA2 genes may cause defective DNA repair and increase the risk for breast cancer. Folate deficiency is associated with increased breast cancer risk and induces chromosome abnormalities. We hypothesized that BRCA1 and BRCA2 germline mutation carriers are more sensitive to the genome damaging effect of folate deficiency compared with healthy non-carrier controls and that this sensitivity is further increased in those carriers who develop breast cancer. We tested these hypotheses in lymphocytes cultured in a medium containing 12 or 120 nM folic acid (FA) for 9 days and measured proliferative capacity and chromosomal instability using the cytokinesis-block micronucleus assay. BRCA1 and BRCA2 mutation carriers with or without breast cancer were not abnormally sensitive to FA deficiency-induced chromosome instability; however, BRCA2 mutation carriers had significantly reduced cell proliferation. FA deficiency reduced cell proliferation and increased micronucleus formation significantly, accounting for 45–59% and 70–75% of the variance in these parameters compared with 0.3–8.5% and 0.2–0.3% contributed by BRCA1 or BRCA2 mutation carrier status, respectively. The results of this study suggest that moderate folate deficiency has a stronger effect on chromosomal instability than BRCA1 or BRCA2 mutations found in breast cancer families.

~ so folate deficiency might be more risky than having a BRCA 1 or BRCA 2 mutation?
Bob

Edit:- but see
http://jn.nutrition.org/cgi/content/full/130/2/129
Folate and Carcinogenesis: An Integrated Scheme
and ~
http://tealady-health.blog.co.uk/2006/09/09/thiamin_transporters~1110229

edit trackback
http://www.blog.co.uk/htsrv/trackback3.php/1139057/68531

http://www.blog.co.uk/htsrv/trackback3.php/1146252/f6a5b

http://www.prodigy.nhs.uk/ProdigyKnowledge/Guidance/GuidanceView.aspx?GuidanceId=37367&TypeId=1

Breast cancer - managing women with a family history

Patient Information Leaflet (PIL) @ ~
http://www.prodigy.nhs.uk/ProdigyKnowledge/PatientInformation/PatientInformationView.aspx?GuidanceId=37367

http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/fs/en

Restrictions on genetic testing and insurance extended to 2011

as of last year ~
Published: Monday 14 March 2005Reference number: 2005/0112