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Cell Cycle Machinery:

Links with Genesis and Treatment of Breast Cancer

  • Chapter
Innovative Endocrinology of Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 630))

Abstract

Loss of normal growth control is a hallmark of cancer. Thus, understanding the mechanisms of tissue-specific, normal growth regulation and the changes that occur during tumorigenesis may provide insights of both diagnostic and therapeutic importance. Control of cell proliferation in the normal mammary gland is steroid hormone (estrogen and progestin)-dependent, involves complex interactions with other hormones, growth factors and cytokines and ultimately converges on activation of three proto-oncogenes (c-Myc, cyclin D1 and cyclin E1) that are rate limiting for the G1 to S phase transition during normal cell cycle progression. Mammary epithelial cell-specific overexpression of these genes induces mammary carcinoma in mice, while cyclin D1 null mice have arrested mammary gland development and are resistant to carcinoma induced by the neu/erbB2 and ras oncogenes. Furthermore, c-Myc, cyclins D1, E1 and E2 are commonly overexpressed in primary breast cancer where elevated expression is often associated with a more aggressive disease phenotype and an adverse patient outcome. This may be due in part to overexpression of these genes conferring resistance to endocrine therapies since in vitro studies provide compelling evidence that overexpression of c-Myc and to a lesser extent cyclin D1 and cyclin E1, attenuate the growth inhibitory effects of SERMS, antiestrogens and progestins in breast cancer cells. Thus, abnormal regulation of the expression of cell cycle molecules, involved in the steroidal control of cell proliferation in the mammary gland, are likely to be directly involved in the development, progression and therapeutic responsiveness of breast cancer. Furthermore, a more detailed understanding of these pathways may identify new targets for therapeutic intervention particularly in endocrine-unresponsive and endocrine-resistant disease.

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Authors and Affiliations

  1. Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, NSW, 2010, Australia

    Robert L. Sutherland

  2. Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia

    Alison J. Butt, C. Elizabeth Caldon, Catriona M. McNeil, Alexander Swarbrick, Elizabeth A. Musgrove & Robert L. Sutherland

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  1. Alison J. Butt
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  2. C. Elizabeth Caldon
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  1. Laboratory of Oncoendocrinology, Professor N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia

    Lev M. Berstein MD, PhD, DMS

  2. Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    Richard J. Santen MD

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© 2008 Landes Bioscience and Springer Science+Business Media

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Butt, A.J., Caldon, C.E., McNeil, C.M., Swarbrick, A., Musgrove, E.A., Sutherland, R.L. (2008). Cell Cycle Machinery:. In: Berstein, L.M., Santen, R.J. (eds) Innovative Endocrinology of Cancer. Advances in Experimental Medicine and Biology, vol 630. Springer, New York, NY. https://doi.org/10.1007/978-0-387-78818-0_12

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