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- McSherry, Elaine A., et al.
(författare)
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JAM-A expression positively correlates with poor prognosis in breast cancer patients
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:6, s. 1343-1351
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Tidskriftsartikel (refereegranskat)abstract
- The cell-cell adhesion protein junctional adhesion molecule-A (JAM-A) influences; epithelial cell morphology and migration. As migration is required for tumor cell invasion and metastasis, we sought to elucidate the role of JAM-A in invasive breast cancer. A breast cancer tissue microarray was analyzed for JAM-A protein expression, in parallel with analysis of JAM-A gene expression data from a breast cancer clinical dataset. Our data demonstrate a novel association between JAM-A gene and protein upregulation and poor prognosis in breast cancer. To mechanistically dissect this process, we used lentiviral technology to stably knock down JAM-A gene expression by shRNA in MCF7 breast cancer cells, which express high-endogenous levels of JAM-A. We also antagonized JAM-A function in wild-type MCF7 cells using an inhibitory antibody that blocks JAM-A dimerization. Knockdown or functional antagonism of JAM-A decreased breast cancer cell migration in scratch-wound assays. Reductions in beta 1-integrin protein levels were observed after JAM-A-knockdown in MCF7 cells, suggesting a mechanism for reduced motility after loss of JAM-A. Consistent with this hypothesis, tissue microarray analysis of beta 1-integrin protein expression in invasive breast cancer tissues revealed a trend toward high beta 1-integrin protein levels being indicative of poor prognosis. Twenty-two percent of patients were observed to coexpress high levels of JAM-A and beta 1-integrin protein, and MDA-MB-231 breast cells stably overexpressing JAM-A showed an increase in beta 1-integrin protein expression. Our results are consistent with a previously unreported role for JAM-A overexpression as a possible mechanism contributing to progression in primary breast cancer; and a potential therapeutic target. (C) 2009 UICC
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| 2. |
- Ryan, Denise, et al.
(författare)
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Topoisomerase I Amplification in Melanoma is Associated with More Advanced Tumours and Poor Prognosis
- 2010
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Ingår i: Pigment Cell and Melanoma Research. - 1755-148X. ; 23:4, s. 542-553
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Tidskriftsartikel (refereegranskat)abstract
- Summary In this study, we used array-comparative genomic hybridisation (aCGH) and fluorescent in situ hybridisation (FISH) to examine genetic aberrations in melanoma cell lines and tissues. aCGH revealed that the most frequent genetic changes found in melanoma cell lines were amplifications on chromosomes 7p and 20q, along with disruptions on Chr 9, 10, 11, 12, 22 and Y. Validation of the results using FISH on tissue microarrays (TMAs) identified TOP1 as being amplified in melanoma tissues. TOP1 amplification was detected in a high percentage (33%) of tumours and was associated with thicker, aggressive tumours. These results show that TOP1 amplification is associated with advanced tumours and poor prognosis in melanoma. These observations open the possibility that TOP1-targeted therapeutics may be of benefit in a particular subgroup of advanced stage melanoma patients.
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