Targeted DNA methylation screen in the mouse mammary genome reveals a parity-induced hypermethylation of igf1r that persists long after parturition

Tiffany A. Katz, Serena G. Liao, Vincent J. Palmieri, Robert K. Dearth, Thushangi N. Pathiraja, Zhiguang Huo, Patricia Shaw, Sarah Small, Nancy E. Davidson, David G. Peters, George C. Tseng, Steffi Oesterreich, Adrian V. Lee

Research output: Contribution to journalArticlepeer-review

Abstract

The most effective natural prevention against breast cancer is an early first full-term pregnancy. Understanding how the protective effect is elicited will inform the development of new prevention strategies. To better understand the role of epigenetics in long-term protection, we investigated parity-inducedDNAmethylation in the mammary gland. FVB mice were bred or remained nulliparous and mammary glands harvested immediately after involution (early) or 6.5 months following involution (late), allowing identification of both transient and persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory features) analysis was performed using the SureSelectXT Mouse Methyl-seq assay and massively parallel sequencing. Two hundred sixty-nine genes were hypermethylated and 128 hypomethylated persistently at both the early and late time points. Pathway analysis of the persistently differentially methylated genes revealed Igf1r to be central to one of the top identified signaling networks, and Igf1r itself was one of the most significantly hypermethylated genes. Hypermethylation of Igf1r in the parousmammary glandwas associated with a reduction of Igf1r mRNA expression. These data suggest that the IGF pathway is regulated at multiple levels during pregnancy and that its modification might be critical in the protective role of pregnancy. This supports the approach of lowering IGF action for prevention of breast cancer, a concept that is currently being tested clinically.

Original languageEnglish (US)
Pages (from-to)1000-1009
Number of pages10
JournalCancer Prevention Research
Volume8
Issue number10
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Targeted DNA methylation screen in the mouse mammary genome reveals a parity-induced hypermethylation of igf1r that persists long after parturition'. Together they form a unique fingerprint.

Cite this