title: Nuclear expression of Rac1 in cervical premalignant lesions and cervical cancer cells.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratorio de Biología Celular del Cáncer, UACQB, Universidad Autónoma de Guerrero, Guerrero, Mexico. ecastaneda@uacqb-guerrero.org.mx
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Mendoza-Catalán
authors.forename: Gema R
authors.initials: GR
authors.lastname: Cristóbal-Mondragón
authors.forename: Jesús
authors.initials: J
authors.lastname: Adame-Gómez
authors.forename: Heidi N
authors.initials: HN
authors.lastname: del Valle-Flores
authors.forename: José Fco
authors.initials: JF
authors.lastname: Coppe
authors.forename: Laura
authors.initials: L
authors.lastname: Sierra-López
authors.forename: Mirna A
authors.initials: MA
authors.lastname: Romero-Hernández
authors.forename: Luz
authors.initials: L
authors.lastname: del Carmen Alarcón-Romero
authors.forename: Berenice
authors.initials: B
authors.lastname: Illades-Aguiar
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañeda-Saucedo
mesh_terms: D000328:Adult; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*; D055815:Young Adult; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C107953:RAC1 protein, human; D019204:GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein