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

Abstract

BackgroundAbnormal 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.MethodsProtein 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).ResultsImmunoreacivity 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.ConclusionRac1 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.

The Cdc42/Rac Nucleotide Exchange Factor Protein β1Pix (Pak-interacting Exchange Factor) Modulates β-Catenin Transcriptional Activity in Colon Cancer Cells

“…Regarding a regulatory role for ␤ 1 Pix in neoplasia, over-expression of Rho-GEFs, including ␤ 1 Pix, was reported for cervical, liver, and renal cancer (52). With particular regard to colon cancer a recent report indicates that the ␤ 1 Pix gene, ARHGEF7, is highly down-regulated in PPAR␥ ligand-treated human colon cancer cells, an action correlated with inhibition of cell migration (53).…”

Vascular endothelial growth factor C expression is closely correlated with lymph node recurrence and poor prognosis in patients with early stage cervical cancer

“…Despite major advances that have been made in therapeutic approaches, most patients ultimately succumb to cancer progression. [3][4][5]23 Lymph node metastasis has been documented as an important unfavourable prognostic factor and a major cause of cancer-related death. 24 Although the lymph nodes of pN0 disease are histologically negative, lymph node recurrence still can develop after radical surgical resection.…”

Neural crest stem cells in melanoma development

“…Taken together, these findings identify Rac1 as a potential novel candidate target for melanoma therapy. Studies of the role of RAC1 in other cancer types, such as breast [47], colorectal [48], testicular [49], gastric [50], cervical [51], and nonsmall cell lung cancer [52] might help to unravel the precise molecular mechanisms underlying RAC1 function in melanoma.…”