Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers

Breast Cancer Research : BCR
Alison K WardDeborah H Anderson

Abstract

CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the unfolded protein response, has recently been identified as a metastasis suppressor in both breast and bladder cancer. Quantitative real time PCR (qPCR) and immunoblotting were used to determine the impact of histone deacetylation and DNA methylation inhibitors on CREB3L1 expression in breast cancer cell lines. Breast cancer cell lines and tumor samples were analyzed similarly, and CREB3L1 gene methylation was determined using sodium bisulfite conversion and DNA sequencing. Immunohistochemistry was used to determine nuclear versus cytoplasmic CREB3L1 protein. Large breast cancer database analyses were carried out to examine relationships between CREB3L1 gene methylation and mRNA expression in addition to CREB3L1 mRNA expression and prognosis. This study demonstrates that the low CREB3L1 expression previously seen in highly metastatic breast cancer cell lines is caused in part by epigenetic silencing. Treatment of several highly metastatic breast cancer cell lines that had low CREB3L1 expression with DNA methyltransferase and histone deacetylase inhibitors induced expression of CREB3L1, both mRNA and protein. In human breast tumors, CREB3L1 mRNA e...Continue Reading

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Citations

Mar 14, 2018·Bioscience Reports·Li-Qiang LiuZong-Mao Zhao
Jan 10, 2018·Frontiers in Molecular Neuroscience·Michael P GreenwoodDavid Murphy
Jul 11, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Jie WuMaolan Li
Feb 7, 2020·Journal of Mammary Gland Biology and Neoplasia·Qian PuHai-Dong Gao
Jun 7, 2017·Breast Cancer Research : BCR·Shari E SmithDeborah H Anderson
Jul 25, 2019·Frontiers in Cell and Developmental Biology·Luciana SampieriCecilia Alvarez
Apr 21, 2020·Journal of the Endocrine Society·Ulla-Maija HaltiaAnniina Färkkilä
Nov 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ayaha YamamotoMasanori Obana
Aug 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Maike BensbergColm E Nestor

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Methods Mentioned

BETA
histone acetylation
Infrared Imaging
PCR
RNA-Seq
ubiquitination
xenografts

Software Mentioned

SAS
Gene
KM plotter
SPSS
pylab
scipy stat
QuantaSoft
cBioPortal
KM
MacVector

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