Jose Russo

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..The results indicate that differentially expressed genes occur during normal human breast lobular differentiation and these changes might persistently modify the genomic signature of the breast epithelia...

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..This is a novel concept that challenges the current knowledge that a chemopreventive agent needs to be given for a long period to suppress a metabolic pathway or abrogate the function of an organ...

..In this article, we concentrate on discussing the role of estrogen receptors and the metabolic activation of 17beta-estradiol (E(2)) as mechanisms of breast cancer initiation...

..However, only when all the other components of milk, (such as lactose, alpha-lactalbumin, casein and milk fat) are coordinately synthesized within the appropriate structure can full differentiation of the mammary gland be acknowledged...

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..The finding that cell proliferation is of importance for cancer initiation, whereas differentiation is a powerful inhibitor, provides novel tools for developing rational strategies for breast cancer prevention and control...

..Comparative studies of normal and neoplastic breast development have unraveled similarities with experimental models that validate the extrapolation of findings for testing hypotheses on the initiation and progression of breast cancer...

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..This in vitro-in vivo model demonstrates the importance of the basal cell type as a stem cell that reconstitutes the branching pattern of the breast and that is also target of a carcinogenic insult leading to transformation and cancer...

..The signature that identifies those women in whom parity has been protective will serve as a molecular biomarker of differentiation for evaluating the potential use of preventive agents...

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..This genomic signature induced by pregnancy could help to predict in which women parity is protective...

..The increase of undifferentiated structures and the changes in the gene expression profile at different ages suggest that prenatal exposure to BPA can affect the susceptibility of the mammary gland to transformation...

..This is a novel concept which challenges the current knowledge that a chemopreventive agent needs to be given for a long period of time to suppress a metabolic pathway or abrogate the function of an organ...

..Our findings provide a new insight into one of the potential roles of ERbeta in human breast cancer...

..Whereas no aneuploidy was observed in any of the transformed cells, the CGH revealed instead that only cells treated with 4-OH-E2 at the highest concentration (3.6 microM) exhibited DNA gains at 8q24, 9q34 and 20q13 and losses at 13q21...

..2. The relevance of these findings is highlighted by the observation that E(2)- and B[a]P-induced genomic alterations in the same loci found in ductal hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma of the breast...

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..ICI182780 did not prevent these mutations, indicating that the carcinogenic effect of E2 is mainly through its reactive metabolites 4-OHE2 and 2-OHE2, with 4-OHE2 and E2 being mutagenic at lower doses than 2-OHE2...

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..3 and 11q24.2-25, respectively These results also indicate that E(2), like the chemical carcinogen BP, induces in HBEC phenotypes indicative of neoplastic transformation...

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..This is the first report demonstrating mutations of MMR genes during the neoplastic transformation of human breast epithelial cells...

..Our results indicate that a protein-truncating mutation in the hPMS2 gene had occurred during the process of cell transformation and tumorigenesis and that truncation is related to a lack of function of this gene...

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..The aim of this study was to elucidate the effect of prenatal exposure to BBP on the morphology, proliferative index, and genomic signature of the rat mammary gland at different ages...

..The results obtained in this study demonstrated that genes regulating cell proliferation, apoptosis, cell trafficking, and DNA repair are significantly affected by hCG in human breast cancer cells in vitro...

..Furthermore, NRG1 exon 1 was partially methylated in 9 out of 14 (64.3%) morphologically normal tissue samples adjacent to invasive carcinomas...

..Gaining better insights into these molecular pathways in TNBC may lead to identification of novel biomarkers and targets for development of diagnostic and therapeutic approaches for prevention and treatment of TNBC...

..Modulators, e.g. ouabain and related digitalis could be useful to develop valuable anti-breast cancer drugs as both Na+, K+-ATPase inhibitors and ER antagonists...

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..Therefore, these data suggest a heretofore unappreciated potential mechanism for the initiation of breast cancer and identify MMTV Env and ITAM-containing proteins in human breast tumors as probable oncoproteins...

..This difference in the expression of alternate splicing of LH/hCG receptor mRNA among the MCF-10F, MCF-7 and MDA-MB-231 cells, may explain the divergent response of these cells to HOXA1 activation by hCG...

..Slight induction of acetylated histone H4 was detected only in the cells treated with inhibin at 100 ng/ml for 12 and 24 h. This study is the first one to demonstrate that these hormones increase the acetylation of histones...

..This signature is indicative of a reduced breast cancer risk and serves as a molecular biomarker of differentiation for evaluating the potential use of chemopreventive agents...

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..9995). These results represent a novel contribution for a more precise correlation between phenotypic and genotypic diversity in cancer cells studied from microdissected paraffin-embedded tissue...

..These results suggest that the breast tissue of women with BRCA1 or BRCA2 mutations could be more susceptible to the effects of BPA...

..A better understanding of the cellular and molecular mechanisms underlying obesogen-associated obesity will lead to new approaches for slow down and/or prevention of the increased trend of obesity associated with exposure to obesogens...

..These programs are offered as models for improving minority recruitment to cancer-control and -treatment trials, and minority access to cancer treatment in general...

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..SATB1 reprogrammes chromatin organization and the transcription profiles of breast tumours to promote growth and metastasis; this is a new mechanism of tumour progression...

..Our data suggest that estrogen mediates endothelial cell stabilization and vessel assembly. These vessel protective effects involve TGF beta 1 and EGFR signaling transduction pathways...

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..The results showed here seem to further classify S100P as a protein that might be involved in the cell cycle imbalance observed during breast carcinogenesis...

..The changes produced by ICI 182,780 alone were attributed to effects other than its well-known anti-estrogenic activity...

..Initiated cells may be promoted by a number of processes, including hormone receptor stimulated proliferation. These results lay the groundwork for assessing risk and preventing disease...

..The strong association between S100P and ER expression highlights the hypothesis about the possible role played by S100P in the very early stages of breast carcinogenesis...

..Measurement of proliferation index by immunohistochemically detectable markers will probably give superior prognostic results in comparison to grade...

..We evaluated whether CR-1 is present in the plasma of patients with breast and colon cancer, and if it can represent a new biomarker for these malignancies...

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..This retrospective study systematically compared mammographic density with histology in women receiving or not receiving menopausal hormone therapy (HT)...

..As homeotic genes play a pivotal role in development, we sought to decipher the expression pattern in both normal breast tissues and in breast carcinomas...

..Studies on epigenetic mechanisms involving DNA methylation and/or the histone code would contribute to a better interpretation of the chromatin supraorganization changes reported herein...

..The phenotypic and genomic changes triggered by estrogen exposure that lead normal cells to tumorigenesis confirm the role of this steroid hormone in cancer initiation...

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..Based on data in the literature, it is also hypothesized that a decreased wild-type p53 level, possibly promoted by the ras transformation, may be associated with the increased AgNOR response...

..This DNA damage can play an important role in the 4-OHE2-induced mutations and transformation of MCF-10F cells to malignant cells...

..This is in contrast to the non-lactating mammary gland where P-cadherin is restricted to myoepithelial cells, and is present at sites of cell-cell contact...

..Thus, although both CYP19 and CYP1B1 are expressed in a high percentage of breast cancers, CYP1B1 is not a major determinant of the disposition of AIs...

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..This knowledge will serve as the basis for establishing novel genomic signatures as intermediate biomarkers for larger preventive clinical trials at the completion of this project. ..

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..The mission of the Center will be accomplished through interactive meetings among the participants of the Center, and other centers participating in this consortium. ..

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..This plan is in line with goals 1 and 3 of the Breast Cancer Progress Review Group to better understand the biology of the normal mammary gland and of precancerous lesions. ..

..The knowledge gained through this exploratory work will establish the basis for more in dept studies in the role of mismatch repair in breast cancer. ..