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Open AccessArticle

Eag1 Gene and Protein Expression in Human Retinoblastoma Tumors and its Regulation by pRb in HeLa Cells

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Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City 07360, Mexico
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Hospital de Pediatría, Unidad de Investigación Médica en Enfermedades Infecciosas, CMN SXXI, IMSS, Mexico City 06720, Mexico
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Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City 07360, Mexico
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Department of Pathology, Hospital Infantil de México Federico Gómez, Secretaría de Salud, Mexico City 06720, Mexico
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Centro de Investigación Clínica Acelerada SC, Mexico City 07020, Mexico
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Departamento de Radioterapia. Hospital Regional de Alta Especialidad del Bajío. León, Gto. 37660, Mexico
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Department of Physiology, Biophysics and Neuroscience, Centro de Investigación y de Estudios Avanzados del I.P.N., Mexico City 07360, Mexico
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Author to whom correspondence should be addressed.
Genes 2020, 11(2), 119; https://doi.org/10.3390/genes11020119
Received: 10 December 2019 / Revised: 12 January 2020 / Accepted: 18 January 2020 / Published: 21 January 2020
(This article belongs to the Special Issue Role of Ion Channel Genes as Targets in Oncology)
Retinoblastoma is the most common pediatric intraocular malignant tumor. Unfortunately, low cure rates and low life expectancy are observed in low-income countries. Thus, alternative therapies are needed for patients who do not respond to current treatments or those with advanced cases of the disease. Ether à-go-go-1 (Eag1) is a voltage-gated potassium channel involved in cancer. Eag1 expression is upregulated by the human papilloma virus (HPV) oncogene E7, suggesting that retinoblastoma protein (pRb) may regulate Eag1. Astemizole is an antihistamine that is suggested to be repurposed for cancer treatment; it targets proteins implicated in cancer, including histamine receptors, ATP binding cassette transporters, and Eag channels. Here, we investigated Eag1 regulation using pRb and Eag1 expression in human retinoblastoma. The effect of astemizole on the cell proliferation of primary human retinoblastoma cultures was also studied. HeLa cervical cancer cells (HPV-positive and expressing Eag1) were transfected with RB1. Eag1 mRNA expression was studied using qPCR, and protein expression was assessed using western blotting and immunochemistry. Cell proliferation was evaluated with an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. RB1 transfection down-regulated Eag1 mRNA and protein expression. The human retinoblastoma samples displayed heterogeneous Eag1 mRNA and protein expression. Astemizole decreased cell proliferation in primary retinoblastoma cultures. Our results suggest that Eag1 mRNA and protein expression was regulated by pRb in vitro, and that human retinoblastoma tissues had heterogeneous Eag1 mRNA and protein expression. Furthermore, our results propose that the multitarget drug astemizole may have clinical relevance in patients with retinoblastoma, for instance, in those who do not respond to current treatments.
Keywords: Eag1 channels; retinoblastoma; astemizole; tumor suppressor; potassium channels; Kv10.1; KCNH1 Eag1 channels; retinoblastoma; astemizole; tumor suppressor; potassium channels; Kv10.1; KCNH1
MDPI and ACS Style

Chávez-López, M.G.; Zúñiga-García, V.; Castro-Magdonel, B.E.; Vera, E.; Garrido, E.; Sánchez-Ramos, J.; Ponce-Castañeda, M.V.; Cabrera-Muñoz, M.L.; Escobar, Y.; Ortiz, C.S.; Hernández-Gallegos, E.; Avalos-Fuentes, A.; Camacho, J. Eag1 Gene and Protein Expression in Human Retinoblastoma Tumors and its Regulation by pRb in HeLa Cells. Genes 2020, 11, 119.

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