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Languages : en
Pages : 21
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One of the principal objectives of our laboratory is to understand the mechanisms by which hormones and growth factors regulate normal mammary gland development, and how these same regulatory pathways become altered in breast cancer. Therefore, specific interest has been placed upon studying the mechanisms by which the lactogenic hormones regulate milk protein gene expression. CAAT/enhancer binding protein beta(C/EBP(beta)), Yin Yang-1 (YY-1), signal transducers and activators or transcription 5 (STAT5), and the glucocorticoid receptor (GR) have been shown to mediate the hormonal and developmental regulation of a beta-casein gene. However, the mechanism by which these transcription factors as well as coactivator proteins coordinately function to promote normal mammary gland development and breast cancer remains undefined. In this study we tested the dynamic of assembly and disassembly of Stat5, GR, C/EBPb and YY-1 at the hormonally activated b-casein promoter as well as at the recently identified mouse b-casein enhancer located 6kb upstream of the transcription start site. Using ChIP analysis we examined the recruitment of coactivator p300 and determined chromatin acetylation and deacetylation status upon hormone treatments. Finally, we established the time course of pol II and phospho-pol II accumulation at the promoter and enhancer sites. Collectively, these data suggest a model for the assembly of multi-protein complex at the b-casein regulatory regions that helps to understand how the signaling pathways regulated by lactogenic hormones and local growth factors are integrated in the nucleus.
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Publisher:
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Category :
Languages : en
Pages : 21
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Book Description
One of the principal objectives of our laboratory is to understand the mechanisms by which hormones and growth factors regulate normal mammary gland development, and how these same regulatory pathways become altered in breast cancer. Therefore, specific interest has been placed upon studying the mechanisms by which the lactogenic hormones regulate milk protein gene expression. CAAT/enhancer binding protein beta(C/EBP(beta)), Yin Yang-1 (YY-1), signal transducers and activators or transcription 5 (STAT5), and the glucocorticoid receptor (GR) have been shown to mediate the hormonal and developmental regulation of a beta-casein gene. However, the mechanism by which these transcription factors as well as coactivator proteins coordinately function to promote normal mammary gland development and breast cancer remains undefined. In this study we tested the dynamic of assembly and disassembly of Stat5, GR, C/EBPb and YY-1 at the hormonally activated b-casein promoter as well as at the recently identified mouse b-casein enhancer located 6kb upstream of the transcription start site. Using ChIP analysis we examined the recruitment of coactivator p300 and determined chromatin acetylation and deacetylation status upon hormone treatments. Finally, we established the time course of pol II and phospho-pol II accumulation at the promoter and enhancer sites. Collectively, these data suggest a model for the assembly of multi-protein complex at the b-casein regulatory regions that helps to understand how the signaling pathways regulated by lactogenic hormones and local growth factors are integrated in the nucleus.
Author: Benjamin S. Leung
Publisher: Springer Science & Business Media
ISBN: 9401180458
Category : Medical
Languages : en
Pages : 296
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Book Description
The concept that hormones influence tumor growth originated in 1889 with the proposal of Albert Schinzinger who suggested that breast cancer is related to the ovaries. Several years later, Sir George Beatson observed that remission of disseminated breast cancer could be achieved in premenopausal patients by performing bilateral oophorectomy. As a result of the contri butions of Hedley Atkins, Charles Huggins and others, additive and ablative hormonal therapies have been widely used for the treatment of advanced breast cancers for several decades. Model systems to study the effects of hormones on growth and regression of breast tumors have been available for many years; however, the complexities of the hormonal environment have rendered in vivo studies difficult in man and experimental animals. Recently, the availability of long-term cultures of breast cancer cells has stimulated many investigators to use these cell lines to unravel the mechanisms of hormone action. Because of the extreme diversity and complexity of advances regarding the endocrinology of the breast and breast cancers, a multi-authored review was deemed necessary. It has been gratifying to receive contributions from many noted scholars. In Volume I of this monograph, the influence of steroid hormones and their antagonists upon normal and neoplastic tissues of the mammary gland are presented. In Volume II, the effects of peptide and other hormones are reviewed.
Author: Margaret C. Neville
Publisher: Springer
ISBN:
Category : Medical
Languages : en
Pages : 656
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Author: Benjamin S. Leung
Publisher: Springer London
ISBN:
Category : Medical
Languages : en
Pages : 328
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Author: Benjamin S Leung
Publisher:
ISBN: 9789401180467
Category :
Languages : en
Pages : 300
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ISBN:
Category :
Languages : en
Pages : 0
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Growth and development of the mammary gland are controlled by the female hormones estrogen and progesterone. These hormones affect breast cancer growth and are targets for hormonal therapy. For this reason, it is important to understand the role of these hormones in the proliferation of mammary epithelial cells. We have characterized how these hormones may be interacting with the cell cycle machinery. The cell cycle machinery orchestrates the events required for cells to proliferate. It is composed of cyclins and their catalytic partners known as cyclin dependent kinases. We have addressed how estrogen and progesterone affect expression and activities of these cell cycle molecules. We have shown that estrogen can induce cyclin D1 expression and activate cyclin E-cdk2 complexes in breast cancer cells. We have also investigated the relationship between progesterone and cyclin D1 using mice lacking either cyclin D1 or the progesterone receptor. Both strains have a defect in mammary gland development We postulated that cyclin Dl may be regulated by progesterone during pregnancy. However, mammary glands lacking cyclin Dl responded to progesterone like nominal mammary glands. In conclusion, we have studied the role of estrogen and progesterone in regulating the cell cycle of mammary epithelial cells. Understanding the growth regulatory mechanisms affected by these hormones may lead to new ways of breast cancer therapy.
Author: Mark Douglas Aupperlee
Publisher:
ISBN:
Category : Breast
Languages : en
Pages : 396
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Author: Andrea Manni
Publisher: Springer Science & Business Media
ISBN: 1592596991
Category : Medical
Languages : en
Pages : 387
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A cutting-edge review of how derangements in the hormonal and growth factor mechanisms controlling normal mammary development lead to breast cancer. Drawing on the multidisciplinary expertise of leading authorities, the book highlights the roles of oncogenes and tumor suppressor genes, spelling out the importance of autocrine/paracrine loops (e.g., stromal epithelial interactions) in supporting breast cancer cell proliferation and the progression to hormone independence. The book's many prominent contributors also illuminate significant recent advances in the biochemistry and physiology of hormone receptors and review the state-of -the-art in the endocrine therapy of breast cancer. Endocrinology of Breast Cancer provides a unique integrated overview of the most significant basic and clinical developments concerning the hormonal aspects of breast cancer.
Author: Marc E. Lippman
Publisher: Springer Science & Business Media
ISBN: 1461539404
Category : Medical
Languages : en
Pages : 455
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Book Description
In Breast Cancer: Cellular and Molecular Biology [Kluwer Academic Pub lishers, 1988], we tried to present an introduction to the emerging basic studies on steroid receptors, oncogenes, and growth factors in the regulation of normal and malignant mammary epithelium. The response to this volume was superb, indicating a tremendous interest in basic growth regulatory mechanisms governing breast cancer and controlling its malignant progres sion. In the two years since its publication, much new and exciting in formation has been published and the full interplay of regulatory mechanisms is now beginning to emerge. We have divided this book into four sections that we hope will unify important concepts and help to crystallize areas of consensus and/or disagreement among a diverse group of basic and clinical scientists working on the disease. The first section is devoted to studies on oncogenes, antioncogenes, proliferation, and tumor prognosis. The first chapter, by Sunderland and McGuire, introduces the characteristics of breast cancer as studied by patho logists to establish prognostic outcome. Of particular interest is a new proto oncogene called HER-2 (or neu), which is rapidly becoming accepted as a valuable new tumor marker of poor prognosis. The second chapter, by Lee Bookstein and Lee, introduces the best known antioncogene, the retinoblas toma antioncogene, whose expression is sometimes lost in breast cancer. Malignant progression appears to be influenced by the balance of proto oncogene and antioncogene expression.
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ISBN: 9780888311276
Category :
Languages : en
Pages :
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