PEG10 is a c-MYC target gene in cancer cells

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

Research output: Contribution to journalArticle

61 Citations (Scopus)

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

Fingerprint

Neoplasm Genes
Genes
Trophoblasts
Breast Neoplasms
Hepatocellular Carcinoma
Prostatic Neoplasms
Mouse mammary tumor virus
Reading Frames
Ductal Carcinoma
Proteins
Chromatin Immunoprecipitation
Hep G2 Cells
Human Mammary Glands
RNA Interference
Site-Directed Mutagenesis
Epigenomics
Introns
Placenta
Transgenic Mice
Prostate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Li, C. M., Margolin, A., Salas, M., Memeo, L., Mansukhani, M., Hibshoosh, H., ... 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

PEG10 is a c-MYC target gene in cancer cells. / Li, Chi Ming; Margolin, Adam; Salas, Martha; Memeo, Lorenzo; Mansukhani, Mahesh; Hibshoosh, Hanina; Szabolcs, Matthias; Klinakis, Apostolos; Tycko, Benjamin.

In: Cancer Research, Vol. 66, No. 2, 15.01.2006, p. 665-672.

Research output: Contribution to journalArticle

Li, CM, Margolin, 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, vol. 66, no. 2, pp. 665-672. https://doi.org/10.1158/0008-5472.CAN-05-1553
Li CM, Margolin A, Salas M, Memeo L, Mansukhani M, Hibshoosh H et al. PEG10 is a c-MYC target gene in cancer cells. Cancer Research. 2006 Jan 15;66(2):665-672. https://doi.org/10.1158/0008-5472.CAN-05-1553
Li, Chi Ming ; Margolin, Adam ; Salas, Martha ; Memeo, Lorenzo ; Mansukhani, Mahesh ; Hibshoosh, Hanina ; Szabolcs, Matthias ; Klinakis, Apostolos ; Tycko, Benjamin. / PEG10 is a c-MYC target gene in cancer cells. In: Cancer Research. 2006 ; Vol. 66, No. 2. pp. 665-672.
@article{ef354384570f4fa5a177ed2300a77abe,
title = "PEG10 is a c-MYC target gene in cancer cells",
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.",
author = "Li, {Chi Ming} and Adam Margolin and Martha Salas and Lorenzo Memeo and Mahesh Mansukhani and Hanina Hibshoosh and Matthias Szabolcs and Apostolos Klinakis and Benjamin Tycko",
year = "2006",
month = "1",
day = "15",
doi = "10.1158/0008-5472.CAN-05-1553",
language = "English (US)",
volume = "66",
pages = "665--672",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "2",

}

TY - JOUR

T1 - PEG10 is a c-MYC target gene in cancer cells

AU - Li, Chi Ming

AU - Margolin, Adam

AU - Salas, Martha

AU - Memeo, Lorenzo

AU - Mansukhani, Mahesh

AU - Hibshoosh, Hanina

AU - Szabolcs, Matthias

AU - Klinakis, Apostolos

AU - Tycko, Benjamin

PY - 2006/1/15

Y1 - 2006/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=31544474013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=31544474013&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-1553

DO - 10.1158/0008-5472.CAN-05-1553

M3 - Article

VL - 66

SP - 665

EP - 672

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 2

ER -