Regulation of Human Cripto-1 Expression by Nuclear Receptors and DNA Promoter Methylation in Human Embryonal and Breast Cancer Cells

Overview

Journal J Cell Physiol

Specialties Cell Biology
Physiology

Date 2012 Nov 7

PMID 23129342

Citations 23

Authors

Caterina Bianco

Nadia P Castro

Christina Baraty

Kelly Rollman

Natalie Held

Maria Cristina Rangel

Hideaki Karasawa

Monica Gonzales

Luigi Strizzi

David S Salomon

Affiliations

Soon will be listed here.

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.

Citing Articles

International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023.

Burris T, de Vera I, Cote I, Flaveny C, Wanninayake U, Chatterjee A Pharmacol Rev. 2023; 75(6):1233-1318.

PMID: 37586884 PMC: 10595025. DOI: 10.1124/pharmrev.121.000436.

Expression and prognostic value of Cripto-1 in early non-small cell lung cancer.

Zhong J, Li L, Zhang Q, Zou J, Liu W, Xu C Clin Respir J. 2023; 17(12):1203-1208.

PMID: 37528674 PMC: 10730460. DOI: 10.1111/crj.13680.

Understanding the role of Cripto-1 in cancer progression and therapeutic strategies.

Zeng Q, Gao Y, Zhou Y Clin Transl Oncol. 2022; 25(5):1135-1144.

PMID: 36456761 DOI: 10.1007/s12094-022-03023-2.

Whence CRIPTO: The Reemergence of an Oncofetal Factor in 'Wounds' That Fail to Heal.

Freeman D, Rodrigues Sousa E, Karkampouna S, Zoni E, Gray P, Salomon D Int J Mol Sci. 2021; 22(18).

PMID: 34576327 PMC: 8472190. DOI: 10.3390/ijms221810164.

Cripto-1 as a Key Factor in Tumor Progression, Epithelial to Mesenchymal Transition and Cancer Stem Cells.

Arnouk H, Yum G, Shah D Int J Mol Sci. 2021; 22(17).

PMID: 34502188 PMC: 8430685. DOI: 10.3390/ijms22179280.

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