CXCL5 regulation of proliferation and migration in human non-small cell lung cancer cells

Epithelial neutrophil-activating peptide-78 (CXCL5), a member of the subgroup of CXC-type chemokine family, is an inflammatory factor involved in the progression of lung cancer, but the underlying mechanism remains unclear. In this study, we investigated the effects of CXCL5 on proliferation and migration in non-small cell lung cancer (NSCLC) using tissue microarrays from NSCLC patients and H460 cells transfected with a CXCL5-interfered lentivirus vector or stimulated with recombinant CXCL5. We observed that the expression of CXCL5 was significantly higher in lung cancer cell lines, and high CXCL5 was associated with high chemokine (C-X-C motif) receptor 2 expression and was significantly associated with poor differentiation. The high expression of CXCL5 was associated with poor NSCLC prognosis and was an independent predictive factor. Furthermore, downregulation of CXCL5 in H460 cells significantly reduced proliferation and migration. Recombinant CXCL5 promoted H460 cell proliferation and movement by activating MAPK/ERK1/2 and PI3K/AKT signaling. Our study elucidates the important role of CXCL5 in the progression and prognosis of NSCLC. These findings suggested that CXCL5 might be a potential biomarker and novel therapeutic target for lung cancer

Bypassing cellular senescence by genetic screening tools

Bypassing cellular senescence is a prerequisite step in the tumorigenic transformation. It has long been known that loss of a key tumour suppressor gene, such as p53 or pRB, is necessary but not sufficient for spontaneous cellular immortalisation. Therefore, there must be additional mutations and/or epigenetic alterations required for immortalisation to occur. Early work on these processes included somatic-cell genetic studies to estimate the number of senescence genes and nowadays are completed by in vivo models and with the requirements to bypass senescence induced by oncogenic transformation in stem cells. These principal studies laid the foundation for the field of senescence/immortalisation but were labour intensive and the results were somewhat limited. Using retroviral-based functional genetic screening, we and others identified universal genes regulating senescence/immortalisation (either by gain or loss of function) and found that some of these genes are widely altered in human tumours. We also explored the molecular mechanisms throughout these genes that regulate senescence and established the causality of the genetic alteration in tumorigenesis. The identification of genes and pathways regulating senescence/immortalisation could provide novel molecular targets for the treatment and/or prevention of cancer (AU)

Identification of the Rock-dependent transcriptome in rodent fibroblasts

Rock proteins are Rho GTPase-dependent serine/ threonine kinases with crucial roles in F-actin dynamics and cell transformation. By analogy with other protein kinase families, it can be assumed that Rock proteins act, at least in part, through the regulation of gene expression events. However, with the exception of some singular transcriptional targets recently identified, the actual impact of these kinases on the overall cell transcriptome remains unknown. To address this issue, we have used a microarray approach to compare the transcriptomes of exponentially growing NIH3T3 cells that had been untreated or treated with Y27632, a well known specific inhibitor for Rock kinase activity. We show here that the Rock pathway promotes a weak impact on the fibroblast transcriptome, since its inhibition only results in changes in the expression of 2.3% of all the genes surveyed in the microarrays. Most Y27632-dependent genes are downregulated at moderate levels, indicating that the Rock pathway predominantly induces the upregulation of transcriptionally active genes. Although functionally diverse, a common functional leitmotiv of Y27632-dependent genes is the implication of their protein products in cytoskeletal-dependent processes. Taken together, these results indicate that Rock proteins can modify cytoskeletal dynamics by acting at post-transcriptional and transcriptional levels. In addition, they suggest that the main target of these serine/threonine kinases is the phosphoproteome and not the transcriptome (AU)

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Efecto antimitogénico de extractos de Pygeum africanum sobre líneas celulares de cáncer de próstata humana y explantes de hiperplasia benigna de próstata / Antimytogenic effect of Pygeum africanum extracts on human prostate cancer cell lines and benign prostatic hyperplasia explants

OBJETIVOS: Analizar el efecto de extractos de Pygeum africanum sobre la proliferación de células de próstata humana, in vitro. MÉTODOS: Líneas celulares tumorales prostáticas, así como células epiteliales derivadas de hiperplasia benigna de próstata fueron puestas en cultivo y tratadas con extractos de P. africanum. El efecto sobre la proliferación celular fue monitorizado mediante incorporación de (3H)-timidina o bromodesoxiuridina y ensayos de citometría de flujo. RESULTADOS: La incubación con extractos de P. africanum, con o sin adición de aminoácidos, inhibe significativamente y de forma dosis-dependiente la proliferación de las líneas celulares derivadas de cáncer de próstata LNCaP, PZ-HPV-7, y CA-HPV-10. En las células PZ-HPV-7, los extractos de P. africanum contrarrestan la acción mitogénica de EGF y bloquean la transición G1 a S del ciclo celular. Los extractos de P. africanum ejercen también una potente acción antimitogénica sobre células epiteliales que derivan de explantes de hiperplasia benigna de próstata. CONCLUSIONES: Los extractos etanólicos de P. africanum tienen un efecto antimitogénico sobre células tumorales prostáticas y sobre células epiteliales derivadas de hiperplasia benigna de próstata. Dicho efecto está asociado a la inhibición de la acción mitogénica de EGF y se acompaña de una disminución de la entrada de las células en la fase S del ciclo celular (AU)