biostudies-literatureDamaschke NANCI NIH HHS5236-5247https://www.ebi.ac.uk/biostudies/studies/S-EPMC9741865biostudies-literatureUnknown77(19)Loss of imprinting (LOI) is an epigenetic event that relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor <i>IGF2</i>, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between <i>IGF2</i> LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF-binding site mutations at the <i>Igf2-H19</i> imprint control region that abolishes CTCF insulator activity, resulting in biallelic <i>Igf2</i> expression that mimics increased levels seen with aging-induced LOI. We found that <i>Igf2</i> LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. EnginCancer researchLoss of <i>Igf2</i> Gene Imprinting in Murine Prostate Promotes Widespread Neoplastic Growth.PMC9741865R01 CA097131Blute MLBhusari SHuang WDamaschke NAAvilla MZhong WJarrard DFYang BfalseLoss of <i>Igf2</i> Gene Imprinting in Murine Prostate Promotes Widespread Neoplastic Growth.Loss of imprinting (LOI) is an epigenetic event that relaxes an allele-specific restriction on gene expression. One gene that experiences LOI is the paracrine insulin-like growth factor <i>IGF2</i>, which occurs commonly in human prostate tissues during aging and tumorigenesis. However, the relationship between <i>IGF2</i> LOI and prostate tumorigenesis has not been established functionally. In this study, we created a mouse model with CTCF-binding site mutations at the <i>Igf2-H19</i> imprint control region that abolishes CTCF insulator activity, resulting in biallelic <i>Igf2</i> expression that mimics increased levels seen with aging-induced LOI. We found that <i>Igf2</i> LOI increased the prevalence and severity of prostatic intraepithelial neoplasia (PIN), a premalignant lesion. Engin2017-01-01T00:00:00Z2017 Oct2025-04-26T02:10:26.108Z2025-04-06T10:24:05.273ZS-EPMC97418652877516910.1158/0008-5472.can-16-308910.1158/0008-5472.CAN-16-3089