Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization

0329667 - BC 2010 RIV US eng J - Journal Article
Novák, Petr - Jensen, T.J. - Garbe, J. - Sampfer, M.R. - Futscher, B. W.
Stepwise DNA Methylation Changes Are Linked to Escape from Defined Proliferation Barriers and Mammary Epithelial Cell Immortalization.
Cancer Research. Roč. 69, č. 12 (2009), s. 5251-5258. ISSN 0008-5472. E-ISSN 1538-7445
Institutional research plan: CEZ:AV0Z50510513
Keywords : Epigenetics * Breast Cancer * DNA methylation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 7.543, year: 2009

We analyzed genome-wide DNA methylation patterns in an isogenic human mammary epithelial cell (HMEC) culture model of transformation. To acquire immortality and malignancy, the cultured finite lifespan HMEC must overcome two distinct proliferation barriers. Our analysis of HMEC transitioning from finite lifespan to malignantly transformed showed that aberrant DNA methylation changes occur in a stepwise fashion early in the transformation process. The first aberrant DNA methylation step coincides with overcoming stasis, and results in few to hundreds of changes, depending on how stasis was overcome. A second step coincides with immortalization and results in hundreds of additional DNA methylation changes regardless of the immortalization pathway. A majority of these DNA methylation changes are also found in malignant breast cancer cells.
Permanent Link: http://hdl.handle.net/11104/0175639