GPER Overexpression in Cervical Cancer Versus Premalignant Lesions: Its Activation Induces Different Forms of Cell Death

Author(s):

Christian D. Hernandez-Silva, Annie Riera-Leal, Pablo C. Ortiz-Lazareno, Luis F. Jave-Suárez, Adrián Ramírez De Arellano, Edgar I. Lopez-Pulido, José G. Macías-Barragan, Margarita Montoya-Buelna, Judith R. Dávila-Rodríguez, Paola Chabay, José F. Muñoz-Valle and Ana L. Pereira-Suárez*   Pages 783 - 791 ( 9 )

Abstract:

<P>Background: The effect of estrogen has been traditionally studied through the modulation of its alpha and beta nuclear receptors; however, the G Protein-Coupled Estrogen Receptor (GPER) has been recently involved in the pathology of numerous tumors. Although the study of GPER in cervical cancer has begun, its contribution still remains to be completely evaluated. </P><P> Objective: The purpose of this work was to determine the expression of this receptor in different degrees of cervical lesions and whether the stimulation with its specific agonist (G-1) modulated mechanisms of cell survival or cell death in cervical cancer cells. </P><P> Methods: Sections of 44 formalin-fixed paraffin-embedded blocks from patients were analyzed by automated immunohistochemistry. After the stimulation with G-1, proliferation was evaluated by the xCELLigence technology, the integrity of the mitochondrial membrane permeability by MitoCaptureTM fluorescence staining, apoptosis by flow cytometry, and senescence by the senescence-associated &#946;-galactosidase kit. </P><P> Results: GPER was widely expressed in cervical cancer but not in its precursor lesions. The staining was predominantly cytoplasmic, although it was also important in the nucleus of the epithelial cells. G-1 inhibited proliferation, decreased the mitochondrial permeability, and increased the percentage of apoptosis in SiHa, HeLa, and C-33A. Only in C-33A, an increase of the cells in necrosis was observed, whereas SiHa was the only cell line in which senescence was evidenced. </P><P> Conclusion: GPER is a receptor associated with cervical cancer that inhibits the growth and induces different mechanisms of death in cells derived from uterine cervical cancer. It suggests that GPER can be considered a pharmacological target that prevents the development of cervical carcinogenesis.</P>

Keywords:

Cervical cancer, G1, GPER, apoptosis, cervical cancer cells, premalignant lesions.

Affiliation:

Laboratorio de Inmunologia, Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Laboratorio de Inmunologia, Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Division de Inmunologia, Centro de Investigacion Biomedica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco, Division de Inmunologia, Centro de Investigacion Biomedica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco, Instituto de Investigacion en Ciencias Biomedicas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Departamento de Clinicas, Centro Universitario de Los Altos, Tepatitlan de Morelos, Universidad de Guadalajara, Guadalajara, Jalisco, Departamento de Ciencias de la Salud CUValles, Universidad de Guadalajara. Guadalajara- Ameca Rd Km. 45.5, Ameca, Jalisco, Laboratorio de Inmunologia, Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Hospital Civil Viejo Fray Antonio Alcalde, Coronel Calderon 777. Col. El Retiro Guadalajara, Jalisco, Molecular Biology Laboratory, Pathology Division, Ricardo Gutierrez Children Hospital, Ciudad de Buenos Aires, Division de Inmunologia, Centro de Investigacion Biomedica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340 Guadalajara, Jalisco, Laboratorio de Inmunologia, Departamento de Fisiologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara

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