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BMC Cancer. 2012; 12: 116.
Published online Mar 23, 2012. doi:  10.1186/1471-2407-12-116
PMCID: PMC3340301
Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells
Miguel A Mendoza-Catalán,1 Gema R Cristóbal-Mondragón,#1 Jesús Adame-Gómez,#1 Heidi N del Valle-Flores,1 José Fco Coppe,2 Laura Sierra-López,2 Mirna A Romero-Hernández,3 Luz del Carmen Alarcón-Romero,3 Berenice Illades-Aguiar,4 and Eduardo Castañeda-Saucedocorresponding author1,5
1Laboratorio de Biología Celular del Cáncer, UACQB, Universidad Autónoma de Guerrero, Guerrero, Mexico
2Unidad de Patología. Hospital Vicente Guerrero, IMSS, Acapulco, Guerrero, Mexico
3Laboratorio de Citopatología, UACQB, Guerrero, Mexico
4Laboratorio de Biomedicina Molecular, UACQB, Guerrero, Mexico
5Laboratorio 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
corresponding authorCorresponding author.
#Contributed equally.
Miguel A Mendoza-Catalán: catalan_mike/at/yahoo.com.mx; Gema R Cristóbal-Mondragón: gemarcm13/at/hotmail.com; Jesús Adame-Gómez: aagj850819/at/hotmail.com; Heidi N del Valle-Flores: vafh86/at/hotmail.com; José Fco Coppe: fcocoppe/at/telcel.blackberry.net; Laura Sierra-López: dra_laurasierra/at/hotmail.com; Mirna A Romero-Hernández: sonambul/at/yahoo.com.mx; Luz del Carmen Alarcón-Romero: luzdelcarmen14/at/gmail.com; Berenice Illades-Aguiar: b.illadesaguiar/at/gmail.com; Eduardo Castañeda-Saucedo: ecastaneda/at/uacqb-guerrero.org.mx
Received August 7, 2011; Accepted March 23, 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
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