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BMC Cancer  2012 

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

DOI: 10.1186/1471-2407-12-116

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

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Abstract:

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).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.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.Cervical cancer is the second most common malignant neoplasia affecting woman worldwide. Infection with High-Risk Human Papillomavirus (HR-HPV) is considered the main risk factor for developing cervical cancer and its precursor lesions [1-3]. Development of cervical Low-grade Squamous Intraepithelial Lesions (L- SIL) and High-grade Squamous Intraepithelial Lesions (H-SIL), and progression to invasive carcinoma, are associated with alterations in the regulation of several cellular processes such as cell cycle progression, apoptosis, and DNA repair [2,4,5]. The HR-HPV oncoproteins E6 and E7 are responsible for many of these alterations, they act by binding to, and/or modifying the expression/activity of a growing number of cellular proteins [6], including p53 [7], pRb [8], p21 [9,10], and p27 [11,12]. Rho-GTPases

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