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Int J Clin Exp Pathol 2013;6(9):1817-1825

Original Article
Cellular retinol binding protein 1 could be a tumor suppressor gene in cervical cancer

Mónica Mendoza-Rodriguez, Hugo Arreola, Alejandra Valdivia, Raúl Peralta, Humberto Serna, Vanessa Villegas, Pablo Romero, Beatriz
Alvarado-Hernández, Lucero Paniagua, Daniel Marrero-Rodríguez, Marco A Meraz, Mauricio Salcedo

Laboratorio de Oncogenómica, Unidad de Investigación Médica en Enfermedades Oncológicas, UMAE Hospital de Oncología, CMN SXXI,
IMSS Av. Cuauhtémoc 330, Col. Doctores, México D.F. 06720; Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios
Avanzados, IPN, México; Clínica de Colposcopía, Hospital General de México, S.S., México. Actual address: AV, Centro Interdisciplinario de
Ciencias de la Salud, Unidad Milpa Alta, Instituto Politécnico Nacional, Méx

Received July 6, 2013; Accepted July 28, 2013; Epub August 15, 2013; Published September 1, 2013

Abstract: Aims: Cervical Cancer (CC) is one of the most important health problems in women. It frequently presents genetic changes at
chromosome region 3q21. This region contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been implicated as an
important element in the development of other types of cancer. The main goal of the present work was to determine the molecular alterations of
CRBP1 and its relationship to CC. Methods: To determine the molecular alterations of CRBP1 gene in CC; twenty-six CC and twenty-six healthy
cervix samples were evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression levels by an immunohistochemistry assay
on tissue microarray, and 3) the methylation status of the CRBP1 promoter region. Results: The increase in CRBP1 copy number was
observed in 10 out of the 26 CC samples analyzed, while healthy cervices samples showed no changes in the copy number. In addition, there
was a lack of expression of the CRBP1 gene in an important number of the CC samples (17/26), and the CRBP1 gene promoter was
methylated in 15/26 of the CC samples. Interestingly, there was a significant association between the lack of expression of the CRBP1 gene
and its methylation status. Conclusions: The data indicates that, both activating and inactivating changes in the CRBP1 gene could be
significant events in the development and progression of CC, and the lack of expression of the CRBP1 protein could be related with to the
development of CC. We believe that there is enough evidence to consider to CRBP1 gene as a tumor suppressor gene for CC.
(IJCEP1307014).

Keywords: Cervical cancer, CRBP1, expression, copy number, suppressor gene

Address correspondence to: Dr. Mauricio Salcedo, Laboratorio de Oncogenómica, Unidad de Investigación Médica en Enfermedades
Oncológicas UMAE Hospital de Oncología, CMN SXXI, IMSS Av. Cuauhtémoc 330, Col. Doctores, México D.F. 06720. Tel: +5530963303; E-mail:
maosal89@yahoo.com