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Open AccessArticle

Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth

Departamento de Biología de Sistemas, Unidad Docente de Bioquímica y Biología Molecular, Universidad de Alcalá, Alcalá de Henares, 28054 Madrid, Spain
Servicio de Urología, Hospital Universitario de Getafe, Fundación para la Investigación Biomédica del Hospital Universitario de Getafe, Universidad Europea de Madrid, Getafe, 28905 Madrid, Spain
Departamento de Biomedicina y Biotecnología, Universidad de Alcalá; Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28054 Madrid, Spain
Medical Oncology Department, Instituto De Investigación Sanitaria La Princesa, HU La Princesa, 28029 Madrid, Spain
Department of Medicine, Universidad Autónoma de Madrid, 28049 Madrid, Spain
Josep Carreras Leukaemia Research Institute (IJC), 08916 Badalona, Catalonia, Spain
Centro de Investigacion Biomedica en Red Cancer (CIBERONC), 28040 Madrid, Spain
Institucio Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Catalonia, Spain
Physiological Sciences Department, School of Medicine and Health Sciences, University of Barcelona (UB), 08028 Barcelona, Catalonia, Spain
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4687;
Received: 7 June 2020 / Revised: 25 June 2020 / Accepted: 29 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Epigenetic Alterations in Age-Associated Diseases and Cancers)
Prostate and breast cancer constitute the most common cancers among men and women worldwide. The aging population is one of the main risk factors for prostate and breast cancer development and accumulating studies link aging with epigenetic changes. Growth factor independence-1 (Gfi1) is a transcriptional repressor with an important role in human malignancies, including leukemia, colorectal carcinoma, and lung cancer, but its role in prostate and breast cancer is unknown. We have found that Gfi1 epigenetic silencing is a common event in prostate and breast cancer. Gfi1 re-expression in prostate and breast cancer cell lines displaying Gfi1 epigenetic silencing decreases cell proliferation, reduced colony formation density, and tumor growth in nude mice xenografts. In addition, we found that Gfi1 repress alpha 1-anti-trypsin (AAT) and alpha 1-anti-chymotrypsin (ACT) expression, two genes with important functions in cancer development, suggesting that Gfi1 silencing promotes tumor growth by increasing AAT and ACT expression in our system. Finally, Gfi1 epigenetic silencing could be a promising biomarker for prostate cancer progression because it is associated with shorter disease-free survival. In conclusion, our findings strongly indicate that Gfi1 epigenetic silencing in prostate and breast cancer could be a crucial step in the development of these two-well characterized endocrine related tumors. View Full-Text
Keywords: prostate cancer; breast cancer; Gfi1; DNA methylation prostate cancer; breast cancer; Gfi1; DNA methylation
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Ashour, N.; Angulo, J.C.; González-Corpas, A.; Orea, M.J.; Lobo, M.V.T.; Colomer, R.; Colás, B.; Esteller, M.; Ropero, S. Epigenetic Regulation of Gfi1 in Endocrine-Related Cancers: A Role Regulating Tumor Growth. Int. J. Mol. Sci. 2020, 21, 4687.

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