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Publication : Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate.

First Author  Fu VX Year  2008
Journal  Cancer Res Volume  68
Issue  16 Pages  6797-802
PubMed ID  18701505 Mgi Jnum  J:139141
Mgi Id  MGI:3807363 Doi  10.1158/0008-5472.CAN-08-1714
Citation  Fu VX, et al. (2008) Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate. Cancer Res 68(16):6797-802
abstractText  Loss of imprinting (LOI) is an epigenetic alteration involving loss of parental origin-specific expression at normally imprinted genes. A LOI for Igf2, a paracrine growth factor, is important in cancer progression. Epigenetic modifications may be altered by environmental factors. However, is not known whether changes in imprinting occur with aging in prostate and other tissues susceptible to cancer development. We found a LOI for Igf2 occurs specifically in the mouse prostate associated with increased Igf2 expression during aging. In older animals, expression of the chromatin insulator protein CTCF and its binding to the Igf2-H19 imprint control region was reduced. Forced down-regulation of CTCF leads to Igf2 LOI. We further show that Igf2 LOI occurs with aging in histologically normal human prostate tissues and that this epigenetic alteration was more extensive in men with associated cancer. This finding may contribute to a postulated field of cancer susceptibility that occurs with aging. Moreover, Igf2 LOI may serve as a marker for the presence of prostate cancer.
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