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EnglishIntercellular junctions promote homotypic cell to cell adhesion and transfer intracellular signals which control cell growth and apoptosis. Junctional adhesion molecule-A (JAM-A) is a transmembrane immunoglobulin located at tight junctions of normal epithelial cells of mammary ducts and glands. In the present paper we show that JAM-A acts as a survival factor for mammary carcinoma cells. JAM-A null mice expressing Polyoma Middle T under MMTV promoter develop significantly smaller mammary tumors than JAM-A positive mice. Angiogenesis and inflammatory or immune infiltrate were not statistically modified in absence of JAM-A but tumor cell apoptosis was significantly increased. Tumor cells isolated from JAM-A null mice or 4T1 cells incubated with JAM-A blocking antibodies showed reduced growth and increased apoptosis which paralleled altered junctional architecture and adhesive function. In a breast cancer clinical data set, tissue microarray data show that JAM-A expression correlates with poor prognosis. Gene expression analysis of mouse tumor samples showed a correlation between genes enriched in human G3 tumors and genes over expressed in JAM-A +/+ mammary tumors. Conversely, genes enriched in G1 human tumors correlate with genes overexpressed in JAM-A2/2 tumors. We conclude that down regulation of JAM-A reduces tumor aggressive behavior by increasing cell susceptibility to apoptosis. JAM-A may be considered a negative prognostic factor and a potential therapeutic target
Abrogation of junctional adhesion molecule-a expression induces cell apoptosis and reduces breast cancer progression / M. Murakami, C. Giampietro, M. Giannotta, M. Corada, I. Torselli, F. Orsenigo, A. Cocito, G. d'Ario, G. Mazzarol, S. Confalonieri, P. P. Di Fiore, E. Dejana. - In: PLOS ONE. - ISSN 1932-6203. - 6:6(2011 Jun 17), p. e21242.e21242.
| Titolo: | Abrogation of junctional adhesion molecule-a expression induces cell apoptosis and reduces breast cancer progression | |
| Autori: | GIAMPIETRO, COSTANZA (Secondo) DI FIORE, PIER PAOLO (Penultimo) DEJANA, ELISABETTA (Ultimo) | |
| Settore Scientifico Disciplinare: | Settore MED/04 - Patologia Generale | |
| Data di pubblicazione: | 17-giu-2011 | |
| Rivista: | ||
| Tipologia: | Article (author) | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1371/journal.pone.0021242 | |
| Appare nelle tipologie: | 01 - Articolo su periodico |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| journal.pone.0021242.pdf | Publisher's version/PDF | Open Access Visualizza/Apri |
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