title: Expression of transcription factor grainyhead-like 2 is diminished in cervical cancer.
abstract: The transcription factor grainyhead-like 2 (GRHL2) is evolutionarily conserved in many different species, and is involved in morphogenesis, epithelial differentiation, and the control of the epithelial-mesenchymal transition. It has also recently been implicated in carcinogenesis, but its role in this remains controversial. Expression of GRHL2 has not previously been reported in cervical cancer, so the present study aimed to characterize GRHL2 expression in cervical cancer-derived cell lines (CCCLs) and cervical tissues with different grades of lesions. Microarray analysis found that the expression of 58 genes was down-regulated in CCCLs compared to HaCaT cells (non-tumorigenic human epithelial cell line). The expression of eight of these genes was validated by quantitative real-time PCR (qPCR), and GRHL2 was found to be the most down-regulated. Western blot assays corroborated that GRHL2 protein levels were strongly down-regulated in CCCLs. Cervical cells from women without cervical lesions were shown to express GRHL2, while immunohistochemistry found that positivity to GRHL2 decreased in cervical cancer tissues. In conclusion, a loss or strong reduction in GRHL2 expression appears to be a characteristic of cervical cancer, suggesting that GRHL2 down-regulation is a necessary step during cervical carcinogenesis. However, further studies are needed to delineate the role of GRHL2 in cervical cancer and during malignant progression.
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico ; Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS)-Universidad de Guadalajara Guadalajara, Jalisco, Mexico.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Torres-Reyes
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico ; Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS)-Universidad de Guadalajara Guadalajara, Jalisco, Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Alvarado-Ruiz
authors.affiliation: Laboratorio de Oncología Genómica, Unidad de Investigación Médica en Enfermedades Oncológicas, Centro Médico Nacional Siglo XXI-IMSS Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Piña-Sánchez
authors.affiliation: Servicio de Patología, Centro Médico Nacional de Occidente-IMSS Guadalajara, Jalisco, Mexico.
authors.forename: María G
authors.initials: MG
authors.lastname: Martínez-Silva
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico ; Programa de Doctorado en Ciencias Biomédicas, Centro Universitario de Ciencias de la Salud (CUCS)-Universidad de Guadalajara Guadalajara, Jalisco, Mexico.
authors.forename: Moisés
authors.initials: M
authors.lastname: Ramos-Solano
authors.affiliation: Escuela de Biología, Universidad Autónoma de Sinaloa. Culiacán Sinaloa, Mexico.
authors.forename: Vicente
authors.initials: V
authors.lastname: Olimón-Andalón
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico.
authors.forename: Pablo C
authors.initials: PC
authors.lastname: Ortiz-Lazareno
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico.
authors.forename: Georgina
authors.initials: G
authors.lastname: Hernández-Flores
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Bravo-Cuellar
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico.
authors.forename: Adriana
authors.initials: A
authors.lastname: Aguilar-Lemarroy
authors.affiliation: División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS) Guadalajara, Jalisco, Mexico.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jave-Suarez
mesh_terms: D063646:Carcinogenesis; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C470830:GRHL2 protein, human; D014157:Transcription Factors
keywords: GRHL2; carcinogenesis; cervical cancer; epithelial-mesenchymal transition; grainyhead-like 2