PEG10 is a c-MYC target gene in cancer cells

Chi Ming Li, Adam A. Margolin, Martha Salas, Lorenzo Memeo, Mahesh Mansukhani, Hanina Hibshoosh, Matthias Szabolcs, Apostolos Klinakis, Benjamin Tycko

Research output: Contribution to journalArticle

64 Scopus citations

Abstract

The product of the imprinted gene paternally expressed gene-10 (PEG10) has been reported to support proliferation in hepatocellular carcinomas, but how this gene is regulated has been an open question. We find that MYC knockdown by RNA interference suppresses PEG10 expression in Panc1 pancreatic carcinoma and HepG2 hepatocellular carcinoma cells and that knockdown of PEG10 inhibits the proliferation of Panc1, HepG2, and Hep3B cells. Conversely, PEG10 was up-regulated by inducing c-MYC expression in a B-lymphocyte cell line. Chromatin immunoprecipitation from Panc1 cells showed c-MYC bound to an E-box-containing region in the PEG1 first intron and site-directed mutagenesis showed that the most proximal E-box is essential for promoter activity. In a mouse mammary tumor virus (MMTV)-MYC transgenic mouse model of breast cancer, most but not all of the mammary carcinomas had strongly increased Peg10 mRNA compared with normal mammary gland. By immunohistochemistry, normal human breast and prostate epithelium was negative for the major isoform [reading frame-1 (RF1)] of PEG10 protein, but this cytoplasmic protein was strongly expressed in a subset of breast carcinomas in situ and invasive ductal carcinomas (∼30%) and in a similar percentage of prostate cancers. As in the mouse model, we found positive, but not absolute, correlations between PEG10 and c-MYC in tissue arrays containing 161 human breast cancers (P < 0.002) and 30 prostate cancers (P = 0.014). Immunostaining of human placenta showed PEG10 and c-MYC proteins coexpressed in proliferating cytotrophoblast and coordinately lost in postmitotic syncytiotrophoblast. These findings link cancer genetics and epigenetics by showing that a classic protooncogene, MYC, acts directly upstream of a proliferation-positive imprinted gene, PEG10.

Original languageEnglish (US)
Pages (from-to)665-672
Number of pages8
JournalCancer Research
Volume66
Issue number2
DOIs
StatePublished - Jan 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Li, C. M., Margolin, A. A., Salas, M., Memeo, L., Mansukhani, M., Hibshoosh, H., Szabolcs, M., Klinakis, A., & Tycko, B. (2006). PEG10 is a c-MYC target gene in cancer cells. Cancer Research, 66(2), 665-672. https://doi.org/10.1158/0008-5472.CAN-05-1553