Open Access Highly Accessed Research article

Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells

Miguel A Mendoza-Catalán1, Gema R Cristóbal-Mondragón1, Jesús Adame-Gómez1, Heidi N del Valle-Flores1, José Fco Coppe2, Laura Sierra-López2, Mirna A Romero-Hernández3, Luz del Carmen Alarcón-Romero3, Berenice Illades-Aguiar4 and Eduardo Castañeda-Saucedo15*

Author Affiliations

1 Laboratorio de Biología Celular del Cáncer, UACQB, Universidad Autónoma de Guerrero, Guerrero, Mexico

2 Unidad de Patología. Hospital Vicente Guerrero, IMSS, Acapulco, Guerrero, Mexico

3 Laboratorio de Citopatología, UACQB, Guerrero, Mexico

4 Laboratorio de Biomedicina Molecular, UACQB, Guerrero, Mexico

5 Laboratorio de Biología Celular del Cáncer. Edificio "F" segundo piso, UACQB, Universidad Autónoma de Guerrero. Ciudad Universitaria, Av. Lázaro Cárdenas s/n, Chilpancingo, Guerrero CP. 39090, Mexico

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BMC Cancer 2012, 12:116  doi:10.1186/1471-2407-12-116

Published: 23 March 2012

Abstract

Background

Abnormal expression of Rho-GTPases has been reported in several human cancers. However, the expression of these proteins in cervical cancer has been poorly investigated. In this study we analyzed the expression of the GTPases Rac1, RhoA, Cdc42, and the Rho-GEFs, Tiam1 and beta-Pix, in cervical pre-malignant lesions and cervical cancer cell lines.

Methods

Protein expression was analyzed by immunochemistry on 102 cervical paraffin-embedded biopsies: 20 without Squamous Intraepithelial Lesions (SIL), 51 Low- grade SIL, and 31 High-grade SIL; and in cervical cancer cell lines C33A and SiHa, and non-tumorigenic HaCat cells. Nuclear localization of Rac1 in HaCat, C33A and SiHa cells was assessed by cellular fractionation and Western blotting, in the presence or not of a chemical Rac1 inhibitor (NSC23766).

Results

Immunoreacivity for Rac1, RhoA, Tiam1 and beta-Pix was stronger in L-SIL and H-SIL, compared to samples without SIL, and it was significantly associated with the histological diagnosis. Nuclear expression of Rac1 was observed in 52.9% L-SIL and 48.4% H-SIL, but not in samples without SIL. Rac1 was found in the nucleus of C33A and SiHa cells but not in HaCat cells. Chemical inhibition of Rac1 resulted in reduced cell proliferation in HaCat, C33A and SiHa cells.

Conclusion

Rac1 is expressed in the nucleus of epithelial cells in SILs and cervical cancer cell lines, and chemical inhibition of Rac1 reduces cellular proliferation. Further studies are needed to better understand the role of Rho-GTPases in cervical cancer progression.

Keywords:
Rho-GTPases; Carcinogenesis; Risk factors; Rac1