Regulation of human Cripto-1 expression by nuclear receptors and DNA promoter methylation in human embryonal and breast cancer cells

Caterina Bianco*, Nadia P. Castro, Christina Baraty, Kelly Rollman, Natalie Held, Maria Cristina Rangel, Hideaki Karasawa, Monica Gonzales, Luigi Strizzi, David S. Salomon

*Corresponding author for this work

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Human Cripto-1 (CR-1) plays an important role in regulating embryonic development while also regulating various stages of tumor progression. However, mechanisms that regulate CR-1 expression during embryogenesis and tumorigenesis are still not well defined. In the present study, we investigated the effects of two nuclear receptors, liver receptor homolog (LRH)-1 and germ cell nuclear factor receptor (GCNF) and epigenetic modifications on CR-1 gene expression in NTERA-2 human embryonal carcinoma cells and in breast cancer cells. CR-1 expression in NTERA-2 cells was positively regulated by LRH-1 through direct binding to a DR0 element within the CR-1 promoter, while GCNF strongly suppressed CR-1 expression in these cells. In addition, the CR-1 promoter was unmethylated in NTERA-2 cells, while T47D, ZR75-1, and MCF7 breast cancer cells showed high levels of CR-1 promoter methylation and low CR-1 mRNA and protein expression. Treatment of breast cancer cells with a demethylating agent and histone deacetylase inhibitors reduced methylation of the CR-1 promoter and reactivated CR-1 mRNA and protein expression in these cells, promoting migration and invasion of breast cancer cells. Analysis of a breast cancer tissue array revealed that CR-1 was highly expressed in the majority of human breast tumors, suggesting that CR-1 expression in breast cancer cell lines might not be representative of in vivo expression. Collectively, these findings offer some insight into the transcriptional regulation of CR-1 gene expression and its critical role in the pathogenesis of human cancer.

Original languageEnglish (US)
Pages (from-to)1174-1188
Number of pages15
JournalJournal of Cellular Physiology
Volume228
Issue number6
DOIs
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Bianco, C., Castro, N. P., Baraty, C., Rollman, K., Held, N., Rangel, M. C., Karasawa, H., Gonzales, M., Strizzi, L., & Salomon, D. S. (2013). Regulation of human Cripto-1 expression by nuclear receptors and DNA promoter methylation in human embryonal and breast cancer cells. Journal of Cellular Physiology, 228(6), 1174-1188. https://doi.org/10.1002/jcp.24271