Inhibitory effect of a Ras homologue member I on pancreatic cancer and its modulation on epithelium growth factor receptor-Ras-Raf-mitogen-activated protein kinase/extracellular regulated protein kinase/1/2 pathway

Department of Gastroenterology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China.
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae 06/2012; 34(3):197-201. DOI: 10.3881/j.issn.1000-503X.2012.03.001
Source: PubMed


To investigate the regulation of epithelium growth factor receptor (EGFR), pan-Ras, and extracellular regulated protein kinase (ERK) with both a ras homologue member I (ARHI) suppression and epithelium growth factor (EGF) stimulation.
After identification and implication, the constructed plasmid pIRES2-EGFP-ARHI was transfected into Panc-1. The untransfected cell was also explored as controls. The growth curve was drawn to indicate the proliferation effect of ARHI. EGFR-ELISA was performed to investigate the expression of EGFR. Western blot analysis was used to investigate the expression of protein MAPK/ERK1/2, pan-Ras in Panc-1.
The proliferation rate of Panc-1 was inhibited by ARHI compared with both empty plasmid and untransfected cell. The amount of EGFR was parallel in both transfected and untrasfected cell but affected by EGF stimulation. The amount of pan-Ras was decreased after ARHI transfection. The optimum concentration of EGF effect on P-ERK was 50 ng/ml.
Both ARHI and EGF play roles in the EGF-EGFR-Ras-Raf-MAPK/ERK1/2 pathway.

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    ABSTRACT: Aplasia Ras homolog member I (ARHI) is associated with human ovarian cancer (HOC) growth and proliferation; however, the mechanisms are unclear. The purpose of this study was to investigate ARHI effects in HOC SKOV3 cells. We transfected SKOV3 cells with PIRES2-EGFP-ARHI and measured growth inhibition rates, cell cycle distribution, apoptosis rates, and expression of P-STAT3 (phosphorylated signal transduction and activators of transcription 3) and P-ERK (phosphorylated extracellular signal regulated protein kinase). Our data showed significant inhibition of growth, significantly increased S-phase arrest and apoptosis rates, and reduction of P-STAT3 and P-ERK1/2 expression levels. We propose the mechanism may involve ARHI-induced phosphorylation of ERK1/2 and STAT3 protein kinases, thereby blocking proliferation signaling pathways, to induce HOC SKOV3 apoptosis.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
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