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Relaxation of Insulin-Like Growth Factor II Imprinting in Prostate Cancer Development

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Final rept. 15 Dec 2001-14 Dec 2004

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A marked propensity for prostate cancer to arises in the peripheral prostate with aging. The Insulin-like Growth Factor-II IGF2 gene is an auto-paracrine growth stimulator that is an important positive modulator of cancer development. IGF2 typically demonstrates monoallelic, or imprinted, expression in adult tissues and indeed this pattern is maintained in the periurethral zone, a region where cancer development is rare. In addition, IGF2 loss of imprinting LOI, as well as increased IGF2 expression, are common attributes of prostate cancer. It is our hypothesis to be tested that an age dependent loss of IGF2 imprinting, resulting from age-dependent changes in DNA methylation, occurs specifically in the peripheral zone of the prostate and contributes to the increased risk for cancer development. To examine temporally when this loss of IGF2 imprinting occurs and the mechanisms underlying it we propose 3 Specific Aims 1 To determine if IGF2 LOI in the peripheral prostate derives from stromal andor epithelial cells 2 To determine whether IGF2 LOI occurs as an age-dependent process in human prostate tissues that are uninvolved with cancer and 3 To examine DNA methylation as a mechanism for any observed changes in the imprint status in prostate tissues. This proposal is significant and unique in testing whether regional epigenetic changes occur in histologically normal prostate tissues that are destined to become neoplastic. We expect to determine whether specific age-related, peripheral zone changes in methylation and imprinting occur in the general population and whether these changes are linked to prostate cancer development.

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  • Medicine and Medical Research

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