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Epigenetic Changes During Cell Transformation

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Epigenetic Alterations in Oncogenesis

Part of the book series: Advances in Experimental Medicine and Biology ((volume 754))

Abstract

Malignant cancer emerges from normal healthy cells in a multistep ­process that involves both genetic and epigenetic lesions. Both genetic and environmental inputs participate in driving the epigenetic changes that occur during human carcinogenesis. The pathologic changes seen in DNA methylation and histone posttranslational modifications are complex, deeply intertwined, and act in concert to produce malignant transformation. To better understand the causes and consequences of the pathoepigenetic changes in cancer formation, a variety of experimentally tractable human cell line model systems that accurately reflect the molecular alterations seen in the clinical disease have been developed. Results from studies using these cell line model systems suggest that early critical epigenetic events occur in a stepwise fashion prior to cell immortalization. These epigenetic steps coincide with the cell’s transition through well-defined cell proliferation barriers of stasis and telomere dysfunction. Following cell immortalization, stressors, such as environmental toxicants, can induce malignant transformation in a process in which the epigenetic changes occur in a smoother progressive fashion, in contrast to the stark stepwise epigenetic changes seen prior to cell immortalization. It is hoped that developing a clearer understanding of the identity, timing, and consequences of these epigenetic lesions will prove useful in future clinical applications that range from early disease detection to therapeutic intervention in malignant cancer.

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Acknowledgments

This work was supported by grants 1U01CA153086-02 and 5P4200494-22 and by the Margaret E. and Fenton L. Maynard Endowment for Breast Cancer Research. Special thanks is given to my collaborator Dr. Martha Stampfer for her insights and enlightenment regarding the biology of human epithelial cells and current lab members working hard on facets of the projects presented herein, Dr. Lukas Vrba and Mr. Paul Severson. Additional thanks are given to all other past and current lab members who have contributed mightily to this scientific enterprise. Finally, I wish to also acknowledge all colleagues in the area of cancer epigenetics whose work informed this chapter, but could not be cited or discussed herein due to time and space.

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  1. Department of Pharmacology and Toxicology, College of Pharmacy and The University of Arizona Cancer Center, The University of Arizona, Tucson, AZ, 85724-5024, USA

    Bernard W. Futscher

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  1. Bernard W. Futscher
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Correspondence to Bernard W. Futscher .

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Editors and Affiliations

  1. University of Nebraska Medical Center, Eppley Institute for Research in Cancer, 985950 Nebraska Medical Center, Omaha, 68198, Nebraska, USA

    Adam R. Karpf

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Futscher, B.W. (2013). Epigenetic Changes During Cell Transformation. In: Karpf, A. (eds) Epigenetic Alterations in Oncogenesis. Advances in Experimental Medicine and Biology, vol 754. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9967-2_9

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