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JAM-A expression po...
JAM-A expression positively correlates with poor prognosis in breast cancer patients
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McSherry, Elaine A. (författare)
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McGee, Sharon F. (författare)
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- Jirström, Karin (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Doyle, Emma M. (författare)
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Brennan, Donal J. (författare)
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- Landberg, Göran (författare)
- Lund University,Lunds universitet,Patologi, Malmö,Forskargrupper vid Lunds universitet,Pathology, Malmö,Lund University Research Groups
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Dervan, Peter A. (författare)
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Hopkins, Ann M. (författare)
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Gallagher, William M. (författare)
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(creator_code:org_t)
- Wiley, 2009
- 2009
- Engelska.
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:6, s. 1343-1351
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- junctional adhesion molecule-A
- breast cancer
- tight junction
- migration
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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