The Jurassic magmatism of the Demerara Plateau (offshore French Guiana) as a remnant of the Sierra Leone hotspot during the Atlantic rifting.

We report the discovery of 173.4 Ma hotspot-related magmatic rocks in the basement of the Demerara Plateau, offshore French Guiana and Suriname. According to plate reconstructions, a single hotspot may be responsible for the magmatic formation of (1) both the Demerara Plateau (between 180 and 170 Ma) and the Guinea Plateau (circa 165 Ma) during the end of the Jurassic rifting of the Central Atlantic; (2) both Sierra Leone and Ceara Rises (mainly from 76 to 68 Ma) during the upper Cretaceous oceanic spreading of the Equatorial Atlantic ocean; (3) the Bathymetrists seamount chain since the upper Cretaceous.

Role of estrogen receptor alpha transcriptional coregulators in tamoxifen resistance in breast cancer.

Tamoxifen is the endocrine agent most commonly used at all stages of breast cancer. Estrogen receptor (ER) alpha, which belongs to the superfamily of nuclear receptors, has been used to identify breast cancer patients who are likely to respond to tamoxifen, but resistance nonetheless occurs in 30-50% of treated ER alpha-positive breast cancer patients. The antiproliferative activity of tamoxifen, relying primarily on its ability to compete with estrogen for the ER alpha ligand binding site in breast tumor tissue, hypotheses forwarded to explain treatment failure include: (1) the existence of a second estrogen receptor (ER beta), (2) an imbalance in estrogen biosynthesis and catabolism, (3) altered bioavailability of tamoxifen, (4) altered cellular trafficking of ER alpha, (5) non genomic effects of ER alpha, directly interacting with several signal transduction pathways, and (6) transcriptional dysregulation of ER alpha target genes, which may involve both genomic (ERE alteration) and non genomic alterations.

Identification of a three-gene expression signature of poor-prognosis breast carcinoma.

Background: The clinical course of breast cancer is difficult to predict on the basis of established clinical and pathological prognostic criteria. Given the genetic complexity of breast carcinomas, it is not surprising that correlations with individual genetic abnormalities have also been disappointing. The use of gene expression profiles could result in more accurate and objective prognostication.

Altered expression pattern of alternatively spliced estrogen receptor beta transcripts in breast carcinoma.

Dysregulation of total estrogen receptor beta (ERbeta) expression has been implicated in breast tumorigenesis. The ERbeta gene yields five exon 8 alternatively spliced transcripts (ERbeta1-5), which encode proteins with different C-terminal amino acids. Individual expression analysis of these transcripts may provide new insights into estrogen signaling in breast cancer.

Evaluation of mRNA expression of estrogen receptor beta and its isoforms in human normal and neoplastic endometrium.

Endometrial cancer is well known to be estrogen-dependent. Two estrogen receptor types, ERalpha and ERbeta, are major mediators of a diversity of biologic functions of estrogen and play an important role in estrogen-dependent tissues and cancers. Cloning of ERbeta was followed by the discovery of a variety of its isoforms.

Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma.

Introduction: Little is known of the function and clinical significance of intratumoral dysregulation of xenobiotic-metabolizing enzyme expression in breast cancer. One molecular mechanism proposed to explain tamoxifen resistance is altered tamoxifen metabolism and bioavailability.

Methods: To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERalpha)-negative and ERalpha-positive breast tumors.

Expression of PEA3/E1AF/ETV4, an Ets-related transcription factor, in breast tumors: positive links to MMP2, NRG1 and CGB expression.

The PEA3/E1AF/ETV4 gene encodes an Ets-related transcription factor that is expressed in the epithelial cells of the mammary gland. Previous reports have shown that PEA3 can up-regulate promoter activities of many genes associated with tumorigenesis. A significant fraction of those encode matrix metalloproteinases (MMP genes) required for degradation of the extracellular matrix.

Expression analysis of DNA methyltransferases 1, 3A, and 3B in sporadic breast carcinomas.

Purpose: Three genes, namely DNA methyltransferase (DNMT) 1, DNMT3A, and DNMT3B, coding for DNMTs that affect promoter methylation status are thought to play an important role in the development of cancers. Little is known of the biological and clinical significance of these genes in human breast cancer.

Experimental Design: We used real-time reverse transcription-PCR assays to quantify the mRNA expression of the three DNMT genes in a series of 130 breast cancer patients.

Expression analysis of estrogen receptor alpha coregulators in breast carcinoma: evidence that NCOR1 expression is predictive of the response to tamoxifen.

Purpose: Dysregulated expression of steroid receptor transcriptional coactivators and corepressors has been implicated in tamoxifen resistance, especially in estrogen receptor (ER) alpha-positive breast cancer patients. Therefore, expression analysis of these ERalpha coregulators may identify new predictors of the response to tamoxifen treatment.

Experimental Design: We measured mRNA levels of 16 coactivator and 11 corepressor genes with a real-time quantitative reverse transcription-PCR method in 14 ERalpha-positive breast tumors.