Current Issue : July - September Volume : 2013 Issue Number : 3 Articles : 5 Articles
Background: The APC tumor suppressor is mutated or downregulated in many tumor types, and is prominently\r\nlocalized to punctate clusters at protrusion tips in migratory cells, such as in astrocytes where it has been\r\nimplicated in directed cell motility. Although APC loss is considered an initiating event in colorectal cancer, for\r\nexample, it is less clear what role APC plays in tumor cell motility and whether loss of APC might be an important\r\npromoter of tumor progression in addition to initiation.\r\nMethods: The localization of APC and �Ÿ-catenin was analyzed in multiple cell lines, including non-transformed\r\nepithelial lines treated with a proteasome inhibitor or TGF�Ÿ to induce an epithelial-to-mesenchymal transition\r\n(EMT), as well as several breast cancer lines, by immunofluorescence. APC expression was knocked down in 4T07\r\nmammary tumor cells using lentiviral-mediated delivery of APC-specific short-hairpin (sh) RNAs, and assessed using\r\nquantitative (q) reverse-transcriptase (RT)-PCR and western blotting. Tumor cell motility was analyzed by performing\r\nwound-filling assays, and morphology via immunofluorescence (IF) and phase-contrast microscopy. Additionally,\r\nproliferation was measured using BrdU incorporation, and TCF reporter assays were performed to determine\r\n�Ÿ-catenin/TCF-mediated transcriptional activity.\r\nResults: APC/�Ÿ-catenin-rich complexes were observed at protrusion ends of migratory epithelial cells treated with a\r\nproteasome inhibitor or when EMT has been induced and in tumor cells with a mesenchymal, spindle-like\r\nmorphology. 4T07 tumor cells with reduced APC levels were significantly less motile and had a more rounded\r\nmorphology; yet, they did not differ significantly in proliferation or �Ÿ-catenin/TCF transcriptional activity.\r\nFurthermore, we found that APC/�Ÿ-catenin-rich complexes at protrusion ends were dependent upon an intact\r\nmicrotubule cytoskeleton.\r\nConclusions: These findings indicate that membrane protrusions with APC/�Ÿ-catenin-containing puncta control the\r\nmigratory potential and mesenchymal morphology of mammary tumor cells and suggest that APC loss during later\r\nstages of tumor progression might impact tumor cell dissemination or colonization....
Background: Despite the increase in cancer incidence in the last years in Serbia, no nation-wide, population-based\r\ncancer epidemiology data have been reported. In this study cancer incidence and mortality rates for Serbia are\r\npresented using nation-wide data from two population-based cancer registries. These rates are additionally\r\ncompared to European and global cancer epidemiology estimates. Finally, predictions on Serbian cancer incidence\r\nand mortality rates are provided.\r\nMethods: Cancer incidence and mortality was collected from the cancer registries of Central Serbia and Vojvodina\r\nfrom 1999 to 2009. Using age-specific regression models, we estimated time trends and predictions for cancer\r\nincidence and mortality for the following five years (2010ââ?¬â??2014). The comparison of Serbian with European and\r\nglobal cancer incidence/mortality rates, adjusted to the world population (ASR-W) was performed using Serbian\r\npopulation-based data and estimates from GLOBOCAN 2008.\r\nResults: Increasing trends in both overall cancer incidence and mortality rates were identified for Serbia. In men,\r\nlung cancer showed the highest incidence (ASR-W 2009: 70.8/100,000), followed by colorectal (ASR-W 2009:\r\n39.9/100,000), prostate (ASR-W 2009: 29.1/100,000) and bladder cancer (ASR-W 2009: 16.2/100,000). Breast cancer\r\nwas the most common form of cancer in women (ASR-W 2009: 70.8/100,000) followed by cervical (ASR-W 2009:\r\n25.5/100,000), colorectal (ASR-W 2009: 21.1/100,000) and lung cancer (ASR-W 2009: 19.4/100,000). Prostate and\r\ncolorectal cancers have been significantly increasing over the last years in men, while this was also observed for\r\nbreast cancer incidence and lung cancer mortality in women. In 2008 Serbia had the highest mortality rate from\r\nbreast cancer (ASR-W 2008: 22.7/100,000), among all European countries while incidence and mortality of cervical,\r\nlung and colorectal cancer were well above European estimates.\r\nConclusion: Cancer incidence and mortality in Serbia has been generally increasing over the past years. For a\r\nnumber of cancer sites, incidence and mortality is alarmingly higher than in the majority of European regions. For\r\nthis increasing trend to be controlled, the management of risk factors that are present among the Serbian\r\npopulation is necessary. Additionally, prevention and early diagnosis are areas where significant improvements\r\ncould still be made....
One of the molecules regulated by the transcription factor, hypoxia inducible factor (HIF), is the hypoxia-responsive\r\nhematopoietic factor, erythropoietin (EPO). This may have relevance to the development of renal cell carcinoma\r\n(RCC), where mutations of the von Hippel-Lindau (VHL) gene are major risk factors for the development of familial\r\nand sporadic RCC. VHL mutations up-regulate and stabilize HIF, which in turn activates many downstream\r\nmolecules, including EPO, that are known to promote angiogenesis, drug resistance, proliferation and progression\r\nof solid tumours. HIFs typically respond to hypoxic cellular environment. While the hypoxic microenvironment plays\r\na critical role in the development and progression of tumours in general, it is of special significance in the case of\r\nRCC because of the link between VHL, HIF and EPO. EPO and its receptor, EPOR, are expressed in many cancers,\r\nincluding RCC. This limits the use of recombinant human EPO (rhEPO) to treat anaemia in cancer patients, because\r\nthe rhEPO may be stimulatory to the cancer. EPO may also stimulate epithelial-mesenchymal transition (EMT) in\r\nRCC, and pathological EMT has a key role in cancer progression. In this mini review, we summarize the current\r\nknowledge of the role of EPO in RCC. The available data, either for or against the use of EPO in RCC patients, are\r\nequivocal and insufficient to draw a definitive conclusion....
Background: MiR-221 is over-expressed in human hepatocellular carcinoma (HCC), but its clinical significance and\r\nfunction in HCC remains uncertain. The aim of the study was to investigate the relationship between miR-221\r\noverexpression and clinicopathological parameters in HCC formalin-fixed paraffin-embedded (FFPE) tissues, and the\r\neffect of miR-221 inhibitor and mimic on different HCC cell lines in vitro.\r\nMethods: MiR-221 expression was detected using real time RT-qPCR in FFPE HCC and the adjacent noncancerous\r\nliver tissues. The relationship between miR-221 level and clinicopathological features was also analyzed.\r\nFurthermore, miR-221 inhibitor and mimic were transfected into HCC cell lines HepB3, HepG2 and SNU449. The\r\neffects of miR-221 on cell growth, cell cycle, caspase activity and apoptosis were also investigated by\r\nspectrophotometry, fluorimetry, fluorescence microscopy and flow cytometry, respectively.\r\nResults: The relative expression of miR-221 in clinical TNM stages III and IV was significantly higher than that in the\r\nstages I and II. The miR-221 level was also upregulated in the metastatic group compared to the nonmetastatic\r\ngroup. Furthermore, miR-221 over-expression was related to the status of tumor capsular infiltration in HCC clinical\r\nsamples. Functionally, cell growth was inhibited, cell cycle was arrested in G1/S-phase and apoptosis was increased\r\nby miR-221 inhibitor in vitro. Likewise, miR-221 mimic accelerated the cell growth.\r\nConclusions: Expression of miR-221 in FFPE tissues could provide predictive significance for prognosis of HCC\r\npatients. Moreover, miR-221 inhibitor could be useful to suppress proliferation and induce apoptosis in HCC cells.\r\nThus miR-221 might be a critical targeted therapy strategy for HCC....
Background: The expression of a specific set of genes controls the different structures of heparan sulfate\r\nproteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The\r\npurpose of this study is to increase knowledge of HSPG alterations in breast cancer.\r\nMethods: Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were\r\nstudied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to\r\nanalyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan\r\ncore proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study\r\nto include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also\r\nused to analyze tissular expression of particular genes showing significant expression differences, of potential\r\ninterest.\r\nResults: No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13\r\ndemonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5\r\ngenes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of\r\nsyndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some\r\n3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of\r\nextracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving\r\nboth the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme\r\nheparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared\r\nrelated to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays\r\nanti-metastatic features, experienced a strong deregulation in all patients analyzed.\r\nConclusions: IDCs show alterations in the expression of HSPG genes; principally the expression and localization of\r\nproteoglycans and the sulfation patterns of glycosaminoglycan chains, depending on the metastatic nature of the\r\ntumor. In addition, the anti-proliferative molecule heparanase 2 experiences strong deregulation, thus highlighting\r\nit as a potentially interesting diagnostic factor....
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